Review ArticleBiologically Active Metabolites Synthesized by Microalgae
Michele Greque de Morais1 Bruna da Silva Vaz1
Etiele Greque de Morais2 and Jorge Alberto Vieira Costa2
1Laboratory of Microbiology and Biochemistry College of Chemistry and Food EngineeringFederal University of Rio Grande PO Box 474 96203-900 Rio Grande RS Brazil2Laboratory of Biochemical Engineering College of Chemistry and Food EngineeringFederal University of Rio Grande PO Box 474 96203-900 Rio Grande RS Brazil
Correspondence should be addressed to Michele Greque de Morais migrequeyahoocombr
Received 19 September 2014 Revised 26 December 2014 Accepted 11 January 2015
Academic Editor Olga Genilloud
Copyright copy 2015 Michele Greque de Morais et al This is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited
Microalgae aremicroorganisms that have differentmorphological physiological and genetic traits that confer the ability to producedifferent biologically active metabolites Microalgal biotechnology has become a subject of study for various fields due to thevaried bioproducts that can be obtained from these microorganismsWhenmicroalgal cultivation processes are better understoodmicroalgae can become an environmentally friendly and economically viable source of compounds of interest because productioncan be optimized in a controlled cultureThe bioactive compounds derived frommicroalgae have anti-inflammatory antimicrobialand antioxidant activities among others Furthermore thesemicroorganisms have the ability to promote health and reduce the riskof the development of degenerative diseases In this context the aim of this review is to discuss bioactive metabolites produced bymicroalgae for possible applications in the life sciences
1 Introduction
Microalgae are unicellularmicroorganisms that grow in freshor salt water and have varied shapes with a diameter or lengthof approximately 3ndash10 120583m The term microalgae includesprokaryotic and eukaryotic organisms [1] Cyanobacteria andbacteria have very similar structural characteristics howeverthey are classified as microalgae because they contain chloro-phyll 119886 and compounds related to photosynthesis The so-called green algae are so named because of the presence ofchlorophyll 119886 and chlorophyll 119887 in the same proportions as inhigher plants [2]
Microalgae are photosynthetic organisms that play a keyrole in aquatic ecosystems Approximately 40of global pho-tosynthesis is due to these microorganisms [3] Microalgalmetabolism reacts to changes in the external environmentwith changes in its intracellular environment Thus themanipulation of the culture conditions or the presence or
absence of certain nutrients stimulates the biosynthesis ofspecific compounds
Several studies have been conducted to investigate theproducts ofmicroalgal metabolism not only to understand itsnature but also to search for substances with possible appli-cations to humans in different fields of interest Screening ofextracts or isolation of metabolites from different microalgaeis a common method for determining the biological activityof these components Microalgae have been described as richsources of various biocompounds of commercial interest [4]
Bioactive compounds ofmicroalgal origin can be sourceddirectly from primary metabolism such as proteins fattyacids vitamins and pigments or can be synthesized fromsecondary metabolism Such compounds can presentantifungal antiviral antialgal antienzymatic or antibioticactions [5]Many of these compounds (cyanovirin oleic acidlinolenic acid palmitoleic acid vitamin E B12 120573-carotenephycocyanin lutein and zeaxanthin) have antimicrobial
Hindawi Publishing CorporationBioMed Research InternationalVolume 2015 Article ID 835761 15 pageshttpdxdoiorg1011552015835761
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Table 1 Principal bioactive compounds extracted from microalgae
antioxidant and anti-inflammatory capacities with thepotential for the reduction and prevention of diseases [6ndash9]In most microalgae the bioactive compounds are accu-mulated in the biomass however in some cases thesemetabolites are excreted into the medium these are knownas exometabolites
Bioactive metabolites of microalgal origin are of specialinterest in the development of new products for medi-cal pharmaceutical cosmetic and food industries Furtherresearch should be conducted with these bioactive com-pounds to verify their beneficial effects for humans theirdegradability when released into the environment and theireffects when used in animals [4] In this context the aim ofthis review is to discuss bioactive metabolites produced bymicroalgae for possible applications in the life sciences
2 Microalgae with Potential for ObtainingBioactive Compounds
Microalgae are a group of heterogeneous microorganismsthat have a great biodiversity of colors shapes and cellcharacteristics and their manipulation is encompassed bythe field of marine biotechnology Among the thousands ofspecies of microalgae believed to exist only a small numberof them are retained in collections around the world andit is estimated that only a few hundreds are investigated forcompounds present in their biomass Of these only and afew are industrially cultivated [9] This untapped diversityresults in potential applications for these microorganisms inseveral biotechnological fields such as the production of
biocompounds used in food medicine cosmetics and phar-maceuticals and even in the energy industry [10]
Microalgae are a natural source of highly interesting bio-logically active compounds These compounds have receivedmuch attention from researchers and companies in recentyears due to their potential applications in different lifescience fields The applications range from the productionof biomass for food and feed to the production of bioactivecompounds for the medical and pharmaceutical industries[9] Considering the enormous biodiversity of microalgaeand recent developments in genetic engineering this groupof microorganisms is one of the most promising sources fornew products and applications [7]
Microalgae are autotrophicmicroorganisms that use lightenergy and inorganic nutrients (carbon dioxide nitrogenphosphorus etc) to develop and synthesize biocompoundsthat have high aggregated nutritional value and therapeuticfunctions such as lipids proteins carbohydrates pigmentsand polymers Recent studies have reported that microalgaecan produce different chemical compounds with differentbiological activities such as carotenoids phycobilins polyun-saturated fatty acids proteins polysaccharides vitamins andsterols among other chemicals [8 11 12]
Components of microalgal origin with antimicrobialantiviral anticoagulant antienzymatic antioxidant antifun-gal anti-inflammatory and anticancer activity among oth-ers were identified [13ndash18] The study of the extractionof bioactive compounds from various microalgae such asArthrospira (Spirulina) Botryococcus braunii Chlorella vul-garis Dunaliella salina Haematococcus pluvialis and Nostoc(Table 1) has been investigated [12 19 20]
BioMed Research International 3
Figure 1 Spirulina sp LEB 18 from LEBFURG strains bank
21 Spirulina Spirulina (Arthrospira) is prokaryotic cyano-bacteria (Figure 1) that belongs to Cyanophyta which arosemore than 3 million years ago forming the current oxygenatmosphere and has been important in the regulation of theplanetary biosphere [21] In 1981 Spirulina was approved bythe FDA (Food Drug Administration) by the issuance of aGRAS (generally recognized as safe) certificate The FDA hasstated that Spirulina can be legally marketed as a food or foodsupplement without risk to human health [22]
Spirulina has a high protein value and high digestibilityand contains significant amounts of essential polyunsaturatedfatty acids and phenolic compounds [23] Due to proper-ties such as its high nutritional value and the presence ofactive biocompounds this microorganism is one of the moststudied microalgae worldwide [24] The Spirulina proteincontent ranges from 50 to 70 (ww) of its dry weight thecarbohydrate content from 10 to 20 (ww) and the lipidcontent from 5 to 10 (ww)
Thismicroalga is rich in vitamins B1 B2 B12 and E (espe-cially vitamin B12) Furthermore Spirulina has a high contentof pigments minerals and oligoelements (approximately 6to 9 (ww) biomass dry weight) of which the most impor-tant are iron calcium magnesium phosphorus and potas-sium [22] Some studies have demonstrated the use of thismicroalga for the production of pigments due to its antiox-idant properties [25ndash27] 120573-Carotene represents approxi-mately 80 of the carotenoids present in Spirulina andother components such as tocopherols phycocyanin andphycoerythrin are also part of its composition [13] Table 2shows some of the bioactive compounds that have beenextracted from Spirulina
Cyanobacteria are known to produce intracellular andextracellular metabolites with potential biological activitiessuch as antibacterial antifungal antiviral antitumor anti-HIV anti-inflammatory antioxidant antimalarial herbici-dal and immunosuppressant effects [13 28 29] The thera-peutic importance of Spirulina has been reported in severalstudies These include its use in the treatment of hyperlipi-demia cancer HIV diabetes obesity and hypertension theimprovement of immune response in renal protection againstheavy metals and drugs and the reduction in serum levels ofglucose and lipids among others [23 27 30 31]
Theworldrsquos largest producer Hainan Simai Pharmacy Co(China) annually produces 3000 tonnes of Spirulina biomass
Figure 2 Microalga Nostoc ellipsosporum from LEBFURG strainsbank
[13] One of the largest industries in the world is EarthriseFarms (California USA) (httpwwwearthrisecom) Manyother companies market a wide variety of nutraceuticalproducts produced from these microalgae For example theMyanmar Spirulina Factory (Yangon Myanmar) producespills French fries and pasta Cyanotech (Hawaii USA)produces and markets products under the name SpirulinaPacifica (httpwwwcyanotechcom) In Brazil the OlsonMicroalgas Macronutricao company (Camaqua Rio Grandedo Sul) produces Spirulina sp LEB 18 capsules for sale as adietary supplement (httpwwwolsoncombr)
22 Nostoc Nostoc is an edible microalga that belongs to theNostocaceae group Cyanophyta that forms spherical coloniesthat link together as filamentsThismicroalga has heterocystswith a pattern of homogeneous cells and a regular distancebetween cells that compose the filament (Figure 2) [32] Theheterocysts fix atmospheric nitrogen for amino acid synthesisin themicroalgal biomass In the absence of a nitrogen sourceduring microalgal cultivation heterocysts form avoiding thelimitation of this nutrient for cell growth [33]
Nostoc microalgal biomass has been used in the medicalfield and as a dietary supplement because of its proteinvitamin and fatty acid content The medical value of thismicroalga was evidenced by its use in the treatment of fistulaand for some forms of cancer [34]Historically the biomass ofthis microorganism is described as anti-inflammatory and italso aids in digestion blood pressure control and immuneboosting Several studies suggest thatNostoc produces severalcompounds with antimicrobial antiviral and anticanceractivity These results have encouraged its cultivation on alarge scale and it has great economic potential due to itsnutritional and pharmaceutical importance [35] Table 3presents some bioactive compounds that have been extractedfrom the microalga of the Nostoc genus
Cyanovirin a potential protein molecule produced by aNostocmicroalga showed a positive effect in the treatment ofHIV [36] and Influenza A (H1N1) [6] Nostoc contains aspectrum of polyunsaturated fatty acids (PUFAs) that includeessential fatty acids such as linoleic 120572-linolenic 120574-linolenicoctadecatetraenoic and eicosapentaenoic acid [37] Essentialfatty acids are precursors of prostaglandins engenderingsignificant interest from the pharmaceutical industry
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Table 2 Bioactive compounds extracted from Spirulina genus
23 Chlorella Spirulina and Chlorella represent the majorityof themicroalgal biomass market with an annual productionof 3000 and 4000 tons respectively [38] Chlorella sp isa eukaryotic genus of green unicellular microalgae thatbelongs to the Chlorophyta group (Figure 3) [39]
This microalga was discovered by the Japanese tradi-tional consumers of algae who usually enjoy it and use itas a food supplement The microalga Chlorella is rich inchlorophyll proteins polysaccharides vitamins mineralsand essential amino acids This microalga is 53 (ww)protein 23 (ww) carbohydrate 9 (ww) lipids and 5(ww) minerals and oligoelements [22]
These nutrient concentrations can be varied by manipu-lation of culture conditions The biomass of this microalga isalso rich in B complex vitamins especially B12 which arevital in the formation and regeneration of blood cells LikeSpirulina Chlorella has a GRAS certificate issued by the FDAand can thus be used as a food without risk to human healthwhen grown in a suitable environment with proper hygieneand good manufacturing practices [22 40]
Chlorella contains bioactive substances with medicinalproperties Experimental studies with Chlorella demon-strated their antitumor anticoagulant antibacterial antiox-idant and antihiperlipidemia effects in addition to a hepato-protective property and the immunostimulatory activity ofenzymatic protein hydrolyzate [39 41ndash44]
Many antioxidant compounds may be responsible forChlorella functional activities Antioxidants such as lutein 120572-carotene 120573-carotene ascorbic acid and 120572-tocopherol whichare active against free radicals were identified Some of thesecompounds not only are important as natural colorants oradditives but also may be useful in reducing the incidence ofcancer and in the prevention ofmacular degeneration [39 45](Table 4)
The most important bioactive compound in Chlorellais 120573-13 glucan an active immunostimulator that reducesfree radicals and blood cholesterol The efficacy of thiscompound against gastric ulcers sores and constipation hasbeen reported It also has been demonstrated to have preven-tive action against atherosclerosis and hypercholesterolemia
BioMed Research International 5
Table 4 Bioactive compounds extracted from the microalgae of the Chlorella genus
as well as antitumor activity [46] Chlorella is produced bymore than 70 companies Taiwan Chlorella ManufacturingCo (Taipei Taiwan) is the worldrsquos largest producer ofChlorella with over 400000 tons of biomass producedper year (httpwwwtaiwanchlorellacomindexphp) Sig-nificant production also occurs in Klotze (Germany) (80ndash100 t yrminus1 of dry biomass) [47]
24 Dunaliella Dunaliella is a green unicellular halotol-erant microalga that belongs to the Chlorophyceae group(Figure 4) This microalga is widely studied due to its tol-erance of extreme habitat conditions physiological aspectsand its many biotechnological applications Dunaliella is asource of carotenoids glycerol lipids and other bioactivecompounds such as enzymes and vitamins [48 49]
This microalga is a major source of natural 120573-caroteneable to produce up to 14 of its dry weight under conditionsof high salinity light and temperature as well as nutrientlimitation [50] In addition to 120573-carotene this microalgais rich in protein and essential fatty acids which can beconsumed safely as evidenced by GRAS recognition [22]Table 5 presents some compounds that have been extractedfrom microalgae of the Dunaliella genus
Compounds in the Dunaliella biomass have various bio-logical activities such as antioxidant antihypertensive bron-chodilatory analgesic muscle relaxant hepatoprotective andantiedemal properties The microalgal biomass can also be
used directly in food and pharmaceutical formulations [2251]
Chang et al [52] showed that Dunaliella cells containedantibiotic substances According to these authors the crudeextract of this microalga strongly inhibited the growthof Staphylococcus aureus Bacillus cereus Bacillus subtilisand Enterobacter aerogenes In another study Dunaliellamicroalga also showed antibacterial activity against variousmicroorganisms of importance to the food industry includ-ing Escherichia coli Staphylococcus aureus Candida albicansand Aspergillus niger [49 53]
Under ideal growing conditions Dunaliella can be stim-ulated to produce approximately 400mg of 120573-carotene persquare meter of growing area The cultivation of Dunaliellafor the production of 120573-carotene has been conducted inseveral countries including Australia Israel the USA andChina [54ndash56] An ingredient of Dunaliella with a strongability to stimulate cell proliferation and improve the energymetabolism of the skin was released by Pentapharm (BaselSwitzerland) [57] New pilot plants are under development inIndia Chile Mexico Cuba Iran Taiwan Japan Spain andKuwait [50]
3 Cultivation Conditions
The conditions for microalgal cultivation are important fac-tors that influence the metabolism of these microorganismsthus directing the synthesis of specific compounds of interestSeveral researchers have noted the influence of incubationtemperature the pH of themedium the period of cultivationaswell as salinity light intensity andmediumconstituents onthe synthesis of antimicrobial agents [58]
31 pH Temperature and Luminescence pH adjustments arethe primary measures used to prevent contamination bymicroorganisms such as other microalgae species pH con-trol is also essential for effective absorption of the compo-nents of the culture medium because it directly affects theavailability of various chemical elements [59] The reductionof some nutrients in the culturemedium can lead the produc-ing of specific biocompounds The difficulty of consuminga nitrogen source for example can lead microalgae to shiftyourmetabolism for lipids or carbohydrates production [60]
Light is an indispensable factor for photosynthesis caus-ing the cells to reproduce and thereby increasing the cell
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Table 5 Bioactive compounds extracted from the microalgae of the Dunaliella genus
concentration [61] The illuminance also influences the bio-chemical composition of the biomass [62] The fatty acidcontent can be reducedwith increasing light incidenceThis isbecause lipids are the major components of chloroplasts andthe increased light energy demand greater activity of chloro-plasts [63] Studies also show the influence of illuminanceon the microalgae antioxidants According to Madhyastha[64] the application of blue light in the cultivation of themicroalga Spirulina fusiformis through a phenomenon wherethe microalgae cells alter the sequence of amino acids withcysteine repeats enhanced the antioxidant capacity
One of the most important factors for the growth of allliving organisms is the temperature The specific growth rateof the microalgae is directly correlated with the gross rate ofCO2
fixationO2
production (photosynthesis) and the respi-ration rate Photosynthesis and respiration are temperature-dependent with the respiration rate increasing exponentiallywith temperature [65] Temperature has a great influenceon the production of biomass proteins lipids and phenoliccompounds from microalgae The optimum temperature forcultivation of microalgae is 35ndash37∘C [66] In studies con-ducted by Noaman [58] that were performed to verifywhich culture conditions stimulated the greatest produc-tion of antimicrobial agents by the microalga Synechococcusleopoliensis it was observed that a temperature of 35∘C andpH 8 produced a maximum concentration of this bioactivecompound
32 Bioreactors Microalgae have attracted much interest forproduction of bioactive compounds and in order to growand tap the potentials of algae efficient photobioreactors arerequired A good number of photobioreactors can be used inproduction of various algal products [67] Innovative culti-vation systems andmodification of biochemical compositionof microalgae by simple changes in the growth media andcultivation conditions (nutrients light intensity temperaturepH mixing etc) can lead to higher productivity of thetargeted products [68]
Bioreactors can be classified as open or closed Closedphotobioreactors have attracted much interest because theyallow a better control of the cultivation conditions than opensystems One of the major advantages of open ponds is thatthey are easier to construct and operate than most closedsystems [67]
In open systems temperature is a main limiting factoras are variations in solar radiation that lead to low biomassconcentrations However open systems are the most widely
used due to their economic viability Closed systems aregenerally used on a pilot scale for investigating problemsrelated to economic viability Furthermore the use of closedsystems is primarily used for microalgal species that do notgrow in a highly selective medium avoiding contaminationof the cultures [69]
Closed bioreactors can provide high productivity gen-erating greater microalgal biomass per unit time Otheradvantages of the use of closed bioreactors compared withopen systems include the following (i) virtually zero losses inconnection with evaporation (ii) a marked reduction ofproblems related to culture contamination by heterotrophicalgae or othermicroorganisms (iii) ease of biomass collectionprocedures due to smaller volumes of culture medium (iv)greater control of gas exchange between the culture andthe atmosphere (v) a smaller occupied space (vi) a highsurfacevolume ratio which helps to increase the illuminationof the system and (vii) the possibility of obtaining high puritycultures [59]
33 Nutrients The metabolism of microalgae can beautotrophic or heterotrophic The former requires onlyinorganic compounds such as CO
2
salts and solar energythe latter is not photosynthetic requiring an external sourceof organic compounds for use as a nutrient and energy sourceSome photosynthetic species are mixotrophic having theability to perform photosynthesis and use exogenous organicsources simultaneously [70]
Microalgae react to changes in their external environmentwith changes in their intracellular environment Thus themanipulation of the culture conditions or the presence orabsence of nutrients stimulates the biosynthesis of specificcompounds This fact was first referenced by Richmond[71] who changed the composition of Chlorella biomassparticularly in their protein and lipid content by varyingcultivation conditions
Noaman [58] found that leucine combined with citrateor acetate is the sources of nitrogen and carbon that pro-duced higher concentrations of antimicrobial agents in themicroalga Synechococcus leopoliensis Coca et al [72] study-ing the cultivation of Spirulina platensis in a medium sup-plemented with vinasse obtained an increased protein yieldcompared to the unsupplemented culture medium Ip andChen [73] studying the cultivation of Chlorella zofingiensisunder mixotrophic cultivation conditions found that lowconcentrations of nitrate and a high glucose concentrationfavored the production of astaxanthin in this microalga
BioMed Research International 7
Alonso et al [74] studying the influence of nitrogen con-centration in continuous cultivation on lipid concentrationin Phaeodactylum tricornutum noted that there was accu-mulation of saturated and unsaturated fatty acids when thenitrogen source was reduced
Culture media are chemical preparations that are formu-lated to contain the nutrients necessary for the microorgan-isms to multiply andor survive The culture media shouldmeet the nutritional needs of the microorganism assist inprocess control and have a reasonably fixed composition[75]
Among different microalgae variations in the culturemedium are mainly related to the amount of necessary nutri-ents Even so nutritional needs are dependent on environ-mental conditions [59] Microalgae require macronutrientssuch as C N O H P Ca Mg S and K for their growthThe micronutrients that are generally required are Fe MnCu Mo and Co Additionally some species require lowerconcentrations of vitamins in the culture medium [76]
4 Advantages of Using Microalgae to ObtainBioactive Compounds
Microalgae are important sources of bioactive natural sub-stances Many metabolites isolated from these microorgan-isms have shown biological activities and potential healthbenefits [77] Microalgae accumulate specific secondarymetabolites (such as pigments and vitamins) which are highvalue products that have applications in the cosmetic foodor pharmaceutical industries [8 78]
Microalgae live in complex habitats and are subjectedto stress andor extreme conditions such as changes insalinity temperature and nutrients Thus these microorgan-isms must rapidly adapt to new environmental conditions tosurvive and thus produce a great variety of biologically activesecondary metabolites that are not found in other organisms[79] Some of the advantages of microalgal cultivation maybe associated with taxonomic diversity the diverse chemicalcomposition the potential for growth in a bioreactor undercontrolled conditions and the ability to produce activesecondary metabolites in response to the stress induced byextreme exposure conditions [39 80]
In addition to their natural characteristics other impor-tant aspects related to microalgae are the use of solar energyand carbon dioxide (CO
2
) and a high growth rate whichcan produce higher yields compared to higher plants Inaddition microalgae can be grown in areas and climates thatare unsuitable for agriculture therefore microalgae do notcompete with arable food production land The possibility ofcontrolling the production of certain bioactive compoundsby manipulation of culture conditions is another advantageof using microalgae [7 81ndash83]
The cultivation of microalgae is a major mechanism forreducing excess carbon dioxide (CO
2
) in the atmosphere bybiofixation in which an industrial process uses a CO
2
-richgas as a carbon source formicroalgal growthThismechanismcontributes to a reduction of the greenhouse effect and globalwarming further reducing the costs of the carbon source
for growth which is the greatest nutrient requirement formicroalgae [13 84]
The cultivation of microalgae is not seasonal they areimportant for food in aquaculture systems and can effectivelyremove pollutants such as nitrogen and phosphorus fromwastewater Moreover they are themost efficient solar energybiomass converters Microalgae cultivation via sunlight-dependent systems contributes to sustainable developmentand natural resource management [13]
The integration of the production process of bioactivemetabolites in a biorefinery is a sustainable means of energyproduction food production and the production of productswith high added value [7] The biorefinery concept based onmicroalgae depends on the efficient use of biomass throughfractionation resulting in several isolated productsThis con-cept encompasses a biorefinery platform which is capable ofoffering a wide variety of different products such as productswith applications in pharmaceuticals medicine food (pro-tein fiber) and biofuels [7 85] These benefits contribute tothe economic viability of microalgal production [7 8]
5 Bioactive Compounds
Bioactive compounds are physiologically active substanceswith functional properties in the human body There is greatenthusiasm for the development and manufacture of variousbiocompounds that can potentially be used as functionalingredients such as carotenoids phycocyanins polyphenolsfatty acids and polyunsaturated compounds [16]
An interest in the production of bioactive compoundsfrom natural sources has recently emerged driven by agrowing number of scientific studies that demonstrate thebeneficial effects of these compounds on health [80] Naturalproducts are important in the search for new pharmaco-logically active compounds In general they play a role indrug discovery for the treatment of human diseases [86]Many clinically viable and commercially available drugs withantitumor and antiinfective activity originated as naturalproducts
Microalgae are a natural source of interesting biocom-pounds Microalgae are known to produce various therapeu-tically effective biocompounds that can be obtained from thebiomass or released extracellularly into the medium [11]These microorganisms contain many bioactive compoundssuch as proteins polysaccharides lipids vitamins enzymessterols and other high-value compounds with pharmaceu-tical and nutritional importance that can be employed forcommercial use [13]
51 Compounds with Antioxidant Function Oxidative dam-age caused by reactive oxygen species to lipids proteins andnucleic acids can cause many chronic diseases such as heartdisease atherosclerosis cancer and aging Epidemiologicalstudies have demonstrated an inverse association between theintake of fruits and vegetables and mortality from diseasessuch as cancer This phenomenon can be attributed to theantioxidant activity of these foods [87]
8 BioMed Research International
Microalgal biomass is considered a rich natural source ofantioxidants with potential applications in food cosmet-ics and medicine [87] Antioxidant compounds such asdimethylsulfoniopropionate and mycosporine amino acidswere isolated frommicroalgae and are potent chemical block-ers ofUV radiation [88] In addition to these compounds pig-ments lipids and polysaccharides with antioxidant activitycan also be found in microalgal biomass
Carotenoids and phycocyanins are the pigments mostused in scientific research C-phycocyanin (C-PC) is a bluephotosynthetic pigment that belongs to the group of phyco-biliproteins found in large quantities in the cyanobacteriaRhodophyta and Cryptophyte [89] Phycocyanin has appli-cations as a nutrient and natural food colorants and cosmet-ics It is usually extracted from the biomass of Spirulina [90]and Porphyridium cruentum [91] and Synechococcus [89]
Among the carotenoid compounds 120573-carotene andastaxanthin are prominent These compounds have appli-cation in the food and pharmaceutical industries becauseof their antioxidant properties and pigmentation ability Inmicroalgal metabolism they protect photosynthetic tissuesagainst damage caused by light and oxygen [92] Dunaliellasalina is a microalga recognized as a major biological sourceof 120573-carotene pigment producing more than 14 in drybiomass [46] H pluvialis is a source of the pigment astax-anthin producing 1ndash8 of astaxanthin as dry biomass [93]
Polysaccharides represent a class of high value-addedcomponents with applications in food cosmetics fabrics sta-bilizers emulsifiers and medicine [94] Microalgal polysac-charides contain sulphate esters are referred to as sulfatedpolysaccharides and possess unique medical applicationsThe basic mechanism of therapeutic action is based on thestimulation of macrophages and modulation The biologicalactivity of sulfur polysaccharides is linked to their sugarcomposition position and degree of sulfation [95] Amongthe microalgae capable of producing these compounds areChlorella vulgaris Scenedesmus quadricauda [96] and Por-phyridium sp [97]
52 Compounds with Antimicrobial Activity The importanceof discovering new compounds with antimicrobial activityis driven by the development of antibiotic resistance inhumans due to constant clinical use of antibioticsMicroalgaeare an important source of antibiotics with a broad andefficient antibacterial activity [11] The antimicrobial activityof these microorganisms is due to the ability to synthesizecompounds such as fatty acids acrylic acids halogenatedaliphatic compounds terpenoids sterols sulfur-containingheterocyclic compounds carbohydrates acetogenins andphenols [98]
The antimicrobial activity of extracts from microalgae isrelated to its lipid composition The antimicrobial action ofmicroalgae is also noteworthy because of the potential toproduce compounds such as 120572- and 120573-ionone 120573-cyclocitralneophytadiene and phytol [99] Microalgae antimicrobialactivity against human pathogens such as Escherichia coliPseudomonas aeruginosa Staphylococcus aureus and Staphy-lococcus epidermidis has been attributed to 120574-linolenic acid
The mechanism of action of fatty acids affects variousstructures in microorganisms however cell membranes arethe most impacted Membrane damage most likely leadsto a loss of internal substances from the cells and theentry of harmful components reduces nutrient absorption inaddition to inhibiting cellular respiration The ability of fattyacids to interfere with bacterial growth depends on boththeir chain length and the degree of unsaturation Fatty acidswith more than 10 carbon atoms apparently induce lysis ofbacterial protoplasts [99]
Microbial polysaccharides and other biological com-pounds have antiviral and antimicrobial action Microalgaeproduce extracellular sulfated polysaccharide (EPS) withacidic characteristics that has a potential as a therapeuticagent [101] Highly sulfated antiviral polysaccharides fromseveral species of microalgae consist mainly of xylose glu-cose and galactose The EPS sulfate groups determine somecharacteristics of polysaccharides it has been found thathigher sulphate contents induced higher antiviral activities[94 101] The inhibitory effect of polysaccharides of microal-gal origin is due to viral interactions or positive charges onthe cell surface thereby preventing penetration of the virusinto host cells [99]
The cyanobacterium Spirulina (Arthrospira) can producesulfated polysaccharides that have already found applicationsas antiviral agents both in vivo and in vitro [102] Eukaryoticmicroalgae such as Chlorella sp and Dunaliella sp produceand secrete polysaccharides at relatively high levels [17] Theantibacterial ability of Spirulina has been correlated withtheir volatile composition resulting in the identification of15 elements which constitutes 96 of total compounds Themajor volatile components produced by Spirulina consist ofheptadecane (40) and tetradecane (35) [39]
Some studies have reported that sulfated polysaccharidesderived from microalgae inhibit viral infection such asencephalomyocarditis virus Herpes simplex virus types 1and 2 (HSV1 HSV2) human immunodeficiency virus (HIV)hemorrhagic septicemia in salmonid virus swine fever virusand varicella virus [99 103] Carrageenan is a sulfatedpolysaccharide that can directly bind to human papillo-mavirus to inhibit not only the viral adsorption process butalso the input and subsequent process of the uncoating of thevirus [101]
53 Compounds with Anti-Inflammatory Action Inflam-mation is an immediate reaction to a cell or tissueinjury caused by noxious stimuli such as toxins andpathogens In this situation the body recognizes theagents responsible for the attack and attempts to neu-tralize them as quickly as possible Inflammation causesredness swelling heat and pain usually located at thesite of infection [104] Ingestion of anti-inflammatory com-pounds enhances the bodyrsquos immune response and helpsto prevent disease and aids the healing process Microal-gae produce several anti-inflammatory compounds in their
BioMed Research International 9
biomass that may exert a protective function in the bodywhen consumed as food or used as pharmaceuticals andcosmetics
Because of its anti-inflammatory capabilities microalgalbiomass is being considered for applications in tissue engi-neering for the development of scaffolds for use in reconsti-tution of organs and tissues [105 106] This is an importantapplication for humans especially in patients with burnsin which the skin was completely lost [107] Among themost important microalgal compounds with such prop-erties are long-chain polyunsaturated fatty acids (PUFAs)[108 109] sulfurized polysaccharides [110] and pigments[111]
Many microalgal polysaccharides possess the ability tomodulate the immune system through the activation ofmacrophage functions and the induction of reactive oxy-gen species (ROS) nitric oxide (NO) and various othertypes of cytokineschemokines [112] Macrophages are ableto regulate several innate responses and secrete cytokinesand chemocytokines that serve as signals for immune andinflammatory molecular reactions [113] Sulfur polysaccha-rides with anti-inflammatory activity can be applied inskin treatments inhibiting the migration and adhesion ofpolymorphonuclear leukocytes [110] Guzman et al [114]studied the anti-inflammatory capacity of the microalgaChlorella stigmatophora and Phaeodactylum tricomutum andconcluded that bothmicroalgae showed positive responses inthe test of paw edema by carrageenan
The PUFAs especially 1205963 and 1205966 as eicosapentaenoic(EPA) docosahexaenoic (DHA) and arachidonic (AA) acidshave been applied in the treatment of chronic inflammationsuch as rheumatism and skin diseases [108] Ryckebosch etal [115] evaluated the nutritional value of the total lipidsextracted from different PUFAs produced by microalgae Inthis study the microalgae IsochrysisNannochloropsis Phaeo-dactylum Pavlova and Thalassiosira produced 1205963 PUFA asan alternative to fish oil in food
Among the pigments with anti-inflammatory activityfucoxanthin carotenoid found in diatoms [116 117] is capableof stimulating apoptosis in human cancer cells [118] A phy-cocyanin found in cyanobacteria has an anti-inflammatoryactivity that occurs through the inhibition of histaminerelease [111 119]
54 Compounds with Potentiality over Degenerative Dis-eases In humans the oxidation reactions driven by reactiveoxygen species (ROS) can lead to irreversible damage tocellular components including lipids proteins and DNAdegradation andor mutation Consequently this damagecan lead to several syndromes such as cardiovascular dis-ease some cancers and the degenerative diseases of aging[120]
Chronic age-related diseases involve oxidative stress andinflammation and their consequences Chronic inflammationplays a significant role in the mediation of neurodegenerativediseases such as Parkinsonrsquos disease Alzheimerrsquos diseasemultiple sclerosis acquired immunodeficiency syndrome(AIDS) and dementia complex [77]
Natural pigments derived from microalgae (NPs) haveneuroprotective properties being valuable sources as func-tional ingredients in foods and pharmaceutical products thatshow efficient action in the treatment andor prevention ofneurodegenerative diseases Vitamin E has preventive effectsfor many diseases such as atherosclerosis and heart diseaseas well as neurodegenerative diseases such as multiplesclerosis [77]
Carotenoids have great potential benefits to humanhealth including the treatment of degenerative diseases suchas macular degeneration and cataract development Thesecompounds act as antioxidants reducing oxidative damageby ROS Studies indicated that increased intake of phenolsdecreased the occurrence of degenerative diseases Phenoliccompounds from microalgae with the potential to fight freeradicals have been reported [121]
Dunaliella salina is a natural source of 120573-carotene whichproduced a reduced risk of cancer and degenerative diseasesin humans Lutein is effective against various diseases includ-ing cataracts and macular degeneration and in the earlystages of atherosclerosis Extracts of Chlorella sp containing120573-carotene and lutein significantly prevented the cognitivedisability that accompanies Alzheimerrsquos disease in rats It wasalso reported that lutein extracted from Chlorella reducedthe incidence of cancer Likewise carotenoids extractedfrom Chlorella ellipsoidea and Chlorella vulgaris inhibited thegrowth of colon cancer [122] A lycopene extracted fromthe microalgae Chlorella marina significantly reduced theproliferation of prostate cancer inmice [123]This compoundalso reduced total cholesterol and low-density lipoprotein(LDL) levels [123] and improved rheumatoid arthritis [124]
Low plasma levels of lutein have also been associatedwith an increased tendency ofmyocardial infarction whereashigh intake of lutein was related to a decreased risk ofstroke In addition high levels of carotenoids with provi-tamin A activity including 120572-carotene 120573-carotene and 120573-cryptoxanthin have been associated with reduction in therisk of angina pectoris Macular degeneration the lead-ing cause of irreversible vision loss has also been associ-ated with very low consumption of lutein and zeaxanthin[125]
Scientific findings indicate astaxanthin for multimodalintervention formany forms of degenerative diseases includ-ing cardiovascular diseases cancer metabolic syndromecognitive impairment age-related immune dysfunctionstomach and ocular diseases (macular degeneration cataractglaucoma diabetic retinopathy and retinitis pigmentosa)and skin damage [126] High levels of lycopene in plasmaand tissues were inversely related to coronary heart diseasemyocardial infarction and the risk of atherosclerosis [125]
55 Compounds withHealth Promoting Function The impor-tance of microalgae as sources of functional ingredients hasbeen recognized because of their beneficial health effectsNatural pigments are valuable sources of bioactive com-pounds These pigments have various beneficial biologicalactivities such as antioxidant anticancer anti-inflammatoryantiobesity antiangiogenic and neuroprotective action and
10 BioMed Research International
are indicated for the treatment or prevention of severalchronic diseases [77]
The antioxidant potential of carotenoid pigments andtheir ability to prevent cancer aging atherosclerosis coro-nary heart disease and degenerative diseases have beendescribed 120573-Carotene has higher provitamin A activitywhich is essential for vision and the correct functioning ofthe immune system Astaxanthin is linked to many healthbenefits such as protection against lipid peroxidation age-related macular degeneration reduced atherosclerosis andan increased immune response [102]
Fucoxanthin is considered as a promising dietary andweight loss supplement and for the treatment of obesityClinical studies by Abidov et al [127] demonstrated the effectof ldquoxanthigenrdquo a fucoxanthin based antiobesity supplementFurthermore fucoxanthinmay be useful for the prevention ofbone diseases such as osteoporosis and rheumatoid arthritisIt has also been reported to be effective for the therapeutictreatment of diabetic diseases suppressing insulin and hyper-glycemia [77]
Microalgae proteins are of great interest as a source ofbioactive peptides due to their therapeutic potential in thetreatment of various diseases [7] Proteins peptides andamino acids have functions that contribute to health benefitsThese compounds can include growth factors hormones andimmunomodulators and can help to replace damaged tissuesin addition to providing nutritional benefits Microalgaesuch as Chlorella and Spirulina (Arthrospira) may be usedas nutraceuticals or included in functional foods to preventdiseases and damage to cells and tissues due to their richprotein content and amino acid profile [102]
The antimicrobial action of certain enzymes (eglysozyme) and immunoglobulins has been reported andrecommended for people with different diseases (egCrohnrsquos disease) due to the existence of formulations withpeptides and free amino acids Studies of the healtheffects of lysozyme have been reported in the microalgaeSpirulina platensis [128] Chlorella [129] and Dunaliellasalina [130] Spirulina (Arthrospira) and Chlorella biomasspills are marketed as is ldquoHawaiian Spirulina Pacificardquo(httpspirulinagreennutritionalscomau) Other proteinscan also increase the production of cholecystokinin involvedin appetite suppression and the reduction of LDL-cholesterolProtein peptides from Chlorella have a potential as dietarysupplements for the prevention of oxidative stress-relateddiseases such as atherosclerosis coronary heart disease andcancer [39]
The essential fatty acids 120596-3 and 120596-6 in particular areimportant for the integrity of tissues 120574-Linolenic acid hastherapeutic applications in cosmetics to revitalize the skinand thus slow aging Linoleic and linolenic acids are essentialnutrients for the immune system and other related tissueregeneration processes Linoleic acid is also used for thetreatment of hyperplasia of the skin [102]
The most studied microalgal lipid compounds are thepolyunsaturated fatty acids (PUFAs) docosahexaenoic acid(120596-3 C226) (DHA) eicosapentaenoic acid (C20 120596-35)(EPA) and arachidonic acid (120596-6 C204) (ARA) Studies haveshown that dietary120596-3 PUFAs have a protective effect against
atherosclerotic heart disease [131] DHA and EPA showed theability to reduce problems associated with strokes and arthri-tis besides reducing hypertension lipid content (a decreasein triglycerides and an increase of HDL) and acting asanti-inflammatory agents DHA is also important in thedevelopment and function of the nervous system Further-more ARA and EPA are platelet aggregators vasoconstric-tors and vasodilators and have antiaggregative action on theendothelium as well as chemostatic activity in neutrophils[102]
Other lipid compounds with interesting bioactive prop-erties are the microalgal sterols Phytosterols have demon-strated reduction of total cholesterol (LDL) in humans byinhibiting its absorption from the intestine [50] Polysac-charides can be considered as dietary fibers associatedwith different physiological effects Insoluble fiber (cellulosehemicellulose and lignin) mainly promotes the movementof material through the digestive system thereby improvinglaxation and increasing satietyThey can also be considered asprebiotics because they promote the growth of gutmicrofloraincluding probiotic species Soluble fiber (oligosaccharidespectins and 120573-glucans) may reduce cholesterol and regulateblood glucose [7 132]
6 Conclusion
The proven ability of microalgae to produce bioactive com-pounds places these microorganisms in the biotechnologicalspotlight for applications in various areas of study especiallyin the life sciencesThe production ofmicroalgal metaboliteswhich stimulate defense mechanisms in the human bodyhas spurred intense study of the application of microalgalbiomass in various foods and pharmacological and medicalproducts There is obviously a need for further study of theidentified compounds and their activities in the treatmentand prevention of various diseases in addition to an ongoingsearch for other as yet undetected metabolites
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgment
The authors thank the National Counsel of Technologicaland Scientific Development (CNPq) for the Productivityin Technological Development and Innovative ExtensionScholarship
References
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[2] A A El Gamal ldquoBiological importance of marine algaerdquo SaudiPharmaceutical Journal vol 18 no 1 pp 1ndash25 2010
BioMed Research International 11
[3] I Moreno-Garrido ldquoMicroalgae immobilization current tech-niques and usesrdquo Bioresource Technology vol 99 no 10 pp3949ndash3964 2008
[4] R-B Volk and F H Furkert ldquoAntialgal antibacterial andantifungal activity of two metabolites produced and excretedby cyanobacteria during growthrdquoMicrobiological Research vol161 no 2 pp 180ndash186 2006
[5] R-B Volk ldquoA newly developed assay for the quantitativedetermination of antimicrobial (anticyanobacterial) activity ofboth hydrophilic and lipophilic test compounds without anyrestrictionrdquoMicrobiological Research vol 163 no 2 pp 161ndash1672008
[6] D F Smee K W Bailey M-H Wong et al ldquoTreatment ofinfluenza A (H1N1) virus infections in mice and ferrets withcyanovirin-Nrdquo Antiviral Research vol 80 no 3 pp 266ndash2712008
[7] E Ibanez and A Cifuentes ldquoBenefits of using algae as naturalsources of functional ingredientsrdquo Journal of the Science of Foodand Agriculture vol 93 no 4 pp 703ndash709 2013
[8] G Markou and E Nerantzis ldquoMicroalgae for high-valuecompounds and biofuels production a review with focus oncultivation under stress conditionsrdquo Biotechnology Advancesvol 31 no 8 pp 1532ndash1542 2013
[9] R Harun M Singh G M Forde andM K Danquah ldquoBiopro-cess engineering ofmicroalgae to produce a variety of consumerproductsrdquo Renewable and Sustainable Energy Reviews vol 14no 3 pp 1037ndash1047 2010
[10] C Kolympiris N Kalaitzandonakes and D Miller ldquoPublicfunds and local biotechnology firm creationrdquo Research Policyvol 43 no 1 pp 121ndash137 2014
[11] S Bhagavathy P Sumathi and I Jancy Sherene Bell ldquoGreenalgae Chlorococcum humicola-a new source of bioactive com-pounds with antimicrobial activityrdquo Asian Pacific Journal ofTropical Biomedicine vol 1 no 1 pp S1ndashS7 2011
[12] A M F Palavra J P Coelho J G Barroso et al ldquoSupercrit-ical carbon dioxide extraction of bioactive compounds frommicroalgae and volatile oils from aromatic plantsrdquo Journal ofSupercritical Fluids vol 60 pp 21ndash27 2011
[13] I Priyadarshani and B Rath ldquoCommercial and industrialapplications of micro algaemdasha reviewrdquo Journal of Algal BiomassUtilization vol 3 no 4 pp 89ndash100 2012
[14] JW Blunt B R CoppM H GMunro P T Northcote andMR Prinsep ldquoMarine natural productsrdquoNatural Product Reportsvol 23 no 1 pp 26ndash78 2006
[15] A M S Mayer and M T Hamann ldquoMarine pharmacologyin 2001-2002 marine compounds with anthelmintic antibacte-rial anticoagulant antidiabetic antifungal anti-inflammatoryantimalarial antiplatelet antiprotozoal antituberculosis andantiviral activities affecting the cardiovascular immune andnervous systems and other miscellaneous mechanisms ofactionrdquo Comparative Biochemistry and Physiology Part C Toxi-cology amp Pharmacology vol 140 no 3-4 pp 265ndash286 2005
[16] M Plaza S Santoyo L Jaime et al ldquoScreening for bioactivecompounds from algaerdquo Journal of Pharmaceutical and Biomed-ical Analysis vol 51 no 2 pp 450ndash455 2010
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vivo and in vitro aspectsrdquo Brazilian Journal of Pharmacognosyvol 23 no 3 pp 471ndash480 2013
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extraction of 120574-linolenic acid and other lipids from Arthrospira(Spirulina)maxima comparison with organic solvent extrac-tionrdquo Food Chemistry vol 99 no 1 pp 57ndash63 2006
[21] I Romano M R Bellitti B Nicolaus et al ldquoLipid profilea useful chemotaxonomic marker for classification of a newcyanobacterium in Spirulina genusrdquo Phytochemistry vol 54 no3 pp 289ndash294 2000
[22] J A C Costa and M G Morais ldquoMicroalgae for food produc-tionrdquo in Fermentation Process Engineering in the Food IndustryC R Soccol A Pandey and C Larroche Eds p 486 Taylor ampFrancis 2013
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[79] I Rodrıguez-Meizoso L Jaime S Santoyo F J Senorans ACifuentes and E Ibanez ldquoSubcritical water extraction andcharacterization of bioactive compounds from Haematococcuspluvialis microalgardquo Journal of Pharmaceutical and BiomedicalAnalysis vol 51 no 2 pp 456ndash463 2010
[80] M Herrero M Castro-Puyana J A Mendiola and E IbanezldquoCompressed fluids for the extraction of bioactive compoundsrdquoTrends in Analytical Chemistry vol 43 pp 67ndash83 2013
[81] N K Singh and D W Dhar ldquoMicroalgae as second generationbiofuel A reviewrdquo Agronomy for Sustainable Development vol31 no 4 pp 605ndash629 2011
[82] L Brennan and P Owende ldquoBiofuels frommicroalgae towardsmeeting advanced fuel standardsrdquo in Advanced Biofuels andBioproducts JW Lee Ed pp 553ndash599 Springer NewYork NYUSA 2013
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production of bioactive compounds from Tetraselmis suecica atpilot scalerdquo Journal of Cleaner Production vol 64 pp 323ndash3312014
[85] B Subhadra ldquoAlgal biorefinery-based industry an approachto address fuel and food insecurity for a carbon-smart worldrdquoJournal of the Science of Food and Agriculture vol 91 no 1 pp2ndash13 2011
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[94] S Arad and O Levy-Ontman ldquoRed microalgal cell-wallpolysaccharides biotechnological aspectsrdquo Current Opinion inBiotechnology vol 21 no 3 pp 358ndash364 2010
[95] M Kim J H Yim S-Y Kim et al ldquoIn vitro inhibitionof influenza A virus infection by marine microalga-derivedsulfated polysaccharide p-KG03rdquoAntiviral Research vol 93 no2 pp 253ndash259 2012
[96] Z A Mohamed ldquoPolysaccharides as a protective responseagainst microcystin-induced oxidative stress in Chlorella vul-garis and Scenedesmus quadricauda and their possible signifi-cance in the aquatic ecosystemrdquo Ecotoxicology vol 17 no 6 pp504ndash516 2008
[97] T Tannin-Spitz M Bergman D Van-Moppes S Grossmanand S Arad ldquoAntioxidant activity of the polysaccharide of thered microalga Porphyridium sprdquo Journal of Applied Phycologyvol 17 no 3 pp 215ndash222 2005
[98] J W Prakash M Johnson and S Jeeva ldquoAntimicrobial activityof certain fresh water microalgae from Thamirabarani RiverTamil Nadu South Indiardquo Asian Pacific Journal of TropicalBiomedicine vol 1 supplement no 2 pp S170ndashS173 2011
[99] H M Amaro A C Guedes and F X Malcata ldquoAntimicrobialactivities of microalgae an invited reviewrdquo in Science againstMicrobial Pathogens Communicating Current Research andTechnological Advances A Mendez-Vilas Ed pp 1272ndash12802011
[100] V J Smith A PDesbois and E ADyrynda ldquoConventional andunconventional antimicrobials from fish marine invertebratesand micro-algaerdquo Marine Drugs vol 8 no 4 pp 1213ndash12622010
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[101] M F D J Raposo A M M B de Morais and R M SC de Morais ldquoInfluence of sulphate on the composition andantibacterial and antiviral properties of the exopolysaccharidefrom Porphyridium cruentumrdquo Life Sciences vol 101 no 1-2 pp56ndash63 2014
[102] M F De Jesus Raposo R M S C De Morais and A M M BDe Morais ldquoHealth applications of bioactive compounds frommarine microalgaerdquo Life Sciences vol 93 no 15 pp 479ndash4862013
[103] A Smelcerovic Z Knezevic-Jugovic and Z PetronijevicldquoMicrobial polysaccharides and their derivatives as current andprospective pharmaceuticalsrdquo Current Pharmaceutical Designvol 14 no 29 pp 3168ndash3195 2008
[104] M T Madigan J M Martinko P V Dunlap and D P ClarkMicrobiologia de Brock Artmed Editora 12th edition 2010
[105] M G de Morais J A V Costa P H L Pranke et alldquoDevelopment of a newnanofiber scaffold for usewith stemcellsin a third degree burn animal modelrdquo Burns Oxford vol 40 no8 pp 1650ndash1660 2014
[106] M G de Morais C Stillings R Dersch et al ldquoPreparation ofnanofibers containing the microalga Spirulina (Arthrospira)rdquoBioresource Technology vol 101 no 8 pp 2872ndash2876 2010
[107] D Steffens M Lersch A Rosa et al ldquoA new biomaterialof nanofibers with the microalga Spirulina as scaffolds tocultivate with stem cells for use in tissue engineeringrdquo Journalof Biomedical Nanotechnology vol 9 no 4 pp 710ndash718 2013
[108] C Barrow and F ShahidiMarine Nutraceuticals and FunctionalFoods CRC Press Taylor amp Francis Boca Raton Fla USA2008
[109] M N A Khan J-Y ChoM-C Lee et al ldquoIsolation of two anti-inflammatory and one pro-inflammatory polyunsaturated fattyacids from the brown seaweed Undaria pinnatifidardquo Journal ofAgricultural and Food Chemistry vol 55 no 17 pp 6984ndash69882007
[110] M S Matsui N Muizzuddin S Arad and K MarenusldquoSulfated polysaccharides from redmicroalgae have antiinflam-matory properties in vitro and in vivordquo Applied Biochemistryand Biotechnology vol 104 no 1 pp 13ndash22 2003
[111] V B Bhat and K M Madyastha ldquoScavenging of peroxynitriteby phycocyanin and phycocyanobilin from Spirulina platensisprotection against oxidative damage to DNArdquo Biochemical andBiophysical Research Communications vol 285 no 2 pp 262ndash266 2001
[112] I A Schepetkin and M T Quinn ldquoBotanical polysaccharidesmacrophage immunomodulation and therapeutic potentialrdquoInternational Immunopharmacology vol 6 no 3 pp 317ndash3332006
[113] J K Park Z-H Kim C G Lee et al ldquoCharacterization andimmunostimulating activity of a water-soluble polysaccharideisolated from Haematococcus lacustrisrdquo Biotechnology and Bio-process Engineering vol 16 no 6 pp 1090ndash1098 2011
[114] S Guzman A Gato M Lamela M Freire-Garabal and J MCalleja ldquoAnti-inflammatory and immunomodulatory activitiesof polysaccharide from Chlorella stigmatophora and Phaeo-dactylum tricornutumrdquo Phytotherapy Research vol 17 no 6 pp665ndash670 2003
[115] E Ryckebosch C Bruneel R Termote-Verhalle K Goiris KMuylaert and I Foubert ldquoNutritional evaluation of microalgaeoils rich in omega-3 long chain polyunsaturated fatty acids as analternative for fish oilrdquo Food Chemistry vol 160 pp 393ndash4002014
[116] P Zhao Z Zang X Xie A Huang and G Wang ldquoTheinfluence of different flocculants on the physiological activityand fucoxanthin production of Phaeodactylum tricornutumrdquoProcess Biochemistry vol 49 no 4 pp 681ndash687 2014
[117] D Moreau C Tomasoni C Jacquot et al ldquoCultivated microal-gae and the carotenoid fucoxanthin from Odontella auritaas potent anti-proliferative agents in bronchopulmonary andepithelial cell linesrdquo Environmental Toxicology and Pharmacol-ogy vol 22 no 1 pp 97ndash103 2006
[118] H Maeda M Hosokawa T Sashima K Funayama and KMiyashita ldquoFucoxanthin from edible seaweed Undaria pinnati-fida shows antiobesity effect through UCP1 expression in whiteadipose tissuesrdquo Biochemical and Biophysical Research Commu-nications vol 332 no 2 pp 392ndash397 2005
[119] J E Piero Estrada P Bermejo Bescos and A M Villar delFresno ldquoAntioxidant activity of different fractions of Spirulinaplatensis protean extractrdquo IL Farmaco vol 56 no 5ndash7 pp 497ndash500 2001
[120] S-M Kang S-J Heo K-N Kim S-H Lee and Y-JJeon ldquoIsolation and identification of new compound 2710158401015840-phloroglucinol-661015840-bieckol from brown algae Ecklonia cavaand its antioxidant effectrdquo Journal of Functional Foods vol 4no 1 pp 158ndash166 2012
[121] HHAbdEl-Baky F K El Baz andG S El-Baroty ldquoProductionof phenolic compounds from Spirulinamaximamicroalgae andits protective effectsrdquoAfrican Journal of Biotechnology vol 8 no24 pp 7059ndash7067 2009
[122] A C Guedes H M Amaro and F X Malcata ldquoMicroalgae assources of carotenoidsrdquoMarineDrugs vol 9 no 4 pp 625ndash6442011
[123] G L Renju G M Kurup and K C H Saritha ldquoEffect oflycopene from Chlorella marina on high cholesterol-inducedoxidative damage and inflammation in ratsrdquo Inflammopharma-cology vol 22 no 1 pp 45ndash54 2014
[124] G L Renju G M Kurup and C H S Kumari ldquoAnti-inflammatory activity of lycopene isolated from Chlorellamarina onType II Collagen induced arthritis in SpragueDawleyratsrdquo Immunopharmacology and Immunotoxicology vol 35 no2 pp 282ndash291 2013
[125] C Vılchez E Forjan M Cuaresma F Bedmar I Garbayo andJ M Vega ldquoMarine carotenoids biological functions andcommercial applicationsrdquo Marine Drugs vol 9 no 3 pp 319ndash333 2011
[126] G Richardson ldquoBeyond eye healthrdquo Life Extension Magazine2011 httpwwwleforgMagazine20117Beyond-Eye-HealthPage-01
[127] M Abidov Z Ramazanov R Seifulla and S Grachev ldquoTheeffects of Xanthigen in the weight management of obesepremenopausal women with non-alcoholic fatty liver diseaseand normal liver fatrdquo Diabetes Obesity and Metabolism vol 12no 1 pp 72ndash81 2010
[128] H M Ragap R H Khalil and H HMutawie ldquoImmunostimu-lant effects of dietary Spirulina platensis on tilapia Oreochromisniloticusrdquo Journal of Applied Pharmaceutical Science vol 2 no2 pp 26ndash31 2012
[129] W Xu Z Gao Z Qi M Qiu J-Q Peng and R Shao ldquoEffect ofdietary chlorella on the growth performance and physiologicalparameters of gibel carp Carassius auratus gibeliordquo TurkishJournal of Fisheries and Aquatic Sciences vol 14 no 1 pp 53ndash572014
[130] P Amaninejad H Emadi M Ematiazjoo et al ldquoEffects ofDunaliella microalgae (Dunaliella salina) on different level of
BioMed Research International 15
IgM Immunoglobulin in rainbow trout (Oncrohynchusmykiss)rdquoGlobal Journal of Biodiversity Science and Management vol 3no 2 pp 237ndash242 2013
[131] V Mimouni L Ulmann V Pasquet et al ldquoThe potential ofmicroalgae for the production of bioactive molecules of phar-maceutical interestrdquoCurrent Pharmaceutical Biotechnology vol13 no 15 pp 2733ndash2750 2012
[132] S M Tosh and S Yada ldquoDietary fibres in pulse seeds and frac-tions characterization functional attributes and applicationsrdquoFood Research International vol 43 no 2 pp 450ndash460 2010
[133] H M Amaro R Barros A C Guedes I Sousa-Pinto and FXMalcata ldquoMicroalgal compoundsmodulate carcinogenesis inthe gastrointestinal tractrdquo Trends in Biotechnology vol 31 no 2pp 92ndash98 2013
[134] S S M Mostafa ldquoMicroalgal biotechnology prospects andapplicationsrdquo in Plant Science chapter 12 pp 275ndash314 InTech2012
[135] L Custodio T Justo L Silvestre et al ldquoMicroalgae of dif-ferent phyla display antioxidant metal chelating and acetyl-cholinesterase inhibitory activitiesrdquoFoodChemistry vol 131 no1 pp 134ndash140 2012
[136] C-CHu J-T Lin F-J Lu F-P Chou andD-J Yang ldquoDetermi-nation of carotenoids in Dunaliella salina cultivated in Taiwanand antioxidant capacity of the algal carotenoid extractrdquo FoodChemistry vol 109 no 2 pp 439ndash446 2008
antioxidant and anti-inflammatory capacities with thepotential for the reduction and prevention of diseases [6ndash9]In most microalgae the bioactive compounds are accu-mulated in the biomass however in some cases thesemetabolites are excreted into the medium these are knownas exometabolites
Bioactive metabolites of microalgal origin are of specialinterest in the development of new products for medi-cal pharmaceutical cosmetic and food industries Furtherresearch should be conducted with these bioactive com-pounds to verify their beneficial effects for humans theirdegradability when released into the environment and theireffects when used in animals [4] In this context the aim ofthis review is to discuss bioactive metabolites produced bymicroalgae for possible applications in the life sciences
2 Microalgae with Potential for ObtainingBioactive Compounds
Microalgae are a group of heterogeneous microorganismsthat have a great biodiversity of colors shapes and cellcharacteristics and their manipulation is encompassed bythe field of marine biotechnology Among the thousands ofspecies of microalgae believed to exist only a small numberof them are retained in collections around the world andit is estimated that only a few hundreds are investigated forcompounds present in their biomass Of these only and afew are industrially cultivated [9] This untapped diversityresults in potential applications for these microorganisms inseveral biotechnological fields such as the production of
biocompounds used in food medicine cosmetics and phar-maceuticals and even in the energy industry [10]
Microalgae are a natural source of highly interesting bio-logically active compounds These compounds have receivedmuch attention from researchers and companies in recentyears due to their potential applications in different lifescience fields The applications range from the productionof biomass for food and feed to the production of bioactivecompounds for the medical and pharmaceutical industries[9] Considering the enormous biodiversity of microalgaeand recent developments in genetic engineering this groupof microorganisms is one of the most promising sources fornew products and applications [7]
Microalgae are autotrophicmicroorganisms that use lightenergy and inorganic nutrients (carbon dioxide nitrogenphosphorus etc) to develop and synthesize biocompoundsthat have high aggregated nutritional value and therapeuticfunctions such as lipids proteins carbohydrates pigmentsand polymers Recent studies have reported that microalgaecan produce different chemical compounds with differentbiological activities such as carotenoids phycobilins polyun-saturated fatty acids proteins polysaccharides vitamins andsterols among other chemicals [8 11 12]
Components of microalgal origin with antimicrobialantiviral anticoagulant antienzymatic antioxidant antifun-gal anti-inflammatory and anticancer activity among oth-ers were identified [13ndash18] The study of the extractionof bioactive compounds from various microalgae such asArthrospira (Spirulina) Botryococcus braunii Chlorella vul-garis Dunaliella salina Haematococcus pluvialis and Nostoc(Table 1) has been investigated [12 19 20]
BioMed Research International 3
Figure 1 Spirulina sp LEB 18 from LEBFURG strains bank
21 Spirulina Spirulina (Arthrospira) is prokaryotic cyano-bacteria (Figure 1) that belongs to Cyanophyta which arosemore than 3 million years ago forming the current oxygenatmosphere and has been important in the regulation of theplanetary biosphere [21] In 1981 Spirulina was approved bythe FDA (Food Drug Administration) by the issuance of aGRAS (generally recognized as safe) certificate The FDA hasstated that Spirulina can be legally marketed as a food or foodsupplement without risk to human health [22]
Spirulina has a high protein value and high digestibilityand contains significant amounts of essential polyunsaturatedfatty acids and phenolic compounds [23] Due to proper-ties such as its high nutritional value and the presence ofactive biocompounds this microorganism is one of the moststudied microalgae worldwide [24] The Spirulina proteincontent ranges from 50 to 70 (ww) of its dry weight thecarbohydrate content from 10 to 20 (ww) and the lipidcontent from 5 to 10 (ww)
Thismicroalga is rich in vitamins B1 B2 B12 and E (espe-cially vitamin B12) Furthermore Spirulina has a high contentof pigments minerals and oligoelements (approximately 6to 9 (ww) biomass dry weight) of which the most impor-tant are iron calcium magnesium phosphorus and potas-sium [22] Some studies have demonstrated the use of thismicroalga for the production of pigments due to its antiox-idant properties [25ndash27] 120573-Carotene represents approxi-mately 80 of the carotenoids present in Spirulina andother components such as tocopherols phycocyanin andphycoerythrin are also part of its composition [13] Table 2shows some of the bioactive compounds that have beenextracted from Spirulina
Cyanobacteria are known to produce intracellular andextracellular metabolites with potential biological activitiessuch as antibacterial antifungal antiviral antitumor anti-HIV anti-inflammatory antioxidant antimalarial herbici-dal and immunosuppressant effects [13 28 29] The thera-peutic importance of Spirulina has been reported in severalstudies These include its use in the treatment of hyperlipi-demia cancer HIV diabetes obesity and hypertension theimprovement of immune response in renal protection againstheavy metals and drugs and the reduction in serum levels ofglucose and lipids among others [23 27 30 31]
Theworldrsquos largest producer Hainan Simai Pharmacy Co(China) annually produces 3000 tonnes of Spirulina biomass
Figure 2 Microalga Nostoc ellipsosporum from LEBFURG strainsbank
[13] One of the largest industries in the world is EarthriseFarms (California USA) (httpwwwearthrisecom) Manyother companies market a wide variety of nutraceuticalproducts produced from these microalgae For example theMyanmar Spirulina Factory (Yangon Myanmar) producespills French fries and pasta Cyanotech (Hawaii USA)produces and markets products under the name SpirulinaPacifica (httpwwwcyanotechcom) In Brazil the OlsonMicroalgas Macronutricao company (Camaqua Rio Grandedo Sul) produces Spirulina sp LEB 18 capsules for sale as adietary supplement (httpwwwolsoncombr)
22 Nostoc Nostoc is an edible microalga that belongs to theNostocaceae group Cyanophyta that forms spherical coloniesthat link together as filamentsThismicroalga has heterocystswith a pattern of homogeneous cells and a regular distancebetween cells that compose the filament (Figure 2) [32] Theheterocysts fix atmospheric nitrogen for amino acid synthesisin themicroalgal biomass In the absence of a nitrogen sourceduring microalgal cultivation heterocysts form avoiding thelimitation of this nutrient for cell growth [33]
Nostoc microalgal biomass has been used in the medicalfield and as a dietary supplement because of its proteinvitamin and fatty acid content The medical value of thismicroalga was evidenced by its use in the treatment of fistulaand for some forms of cancer [34]Historically the biomass ofthis microorganism is described as anti-inflammatory and italso aids in digestion blood pressure control and immuneboosting Several studies suggest thatNostoc produces severalcompounds with antimicrobial antiviral and anticanceractivity These results have encouraged its cultivation on alarge scale and it has great economic potential due to itsnutritional and pharmaceutical importance [35] Table 3presents some bioactive compounds that have been extractedfrom the microalga of the Nostoc genus
Cyanovirin a potential protein molecule produced by aNostocmicroalga showed a positive effect in the treatment ofHIV [36] and Influenza A (H1N1) [6] Nostoc contains aspectrum of polyunsaturated fatty acids (PUFAs) that includeessential fatty acids such as linoleic 120572-linolenic 120574-linolenicoctadecatetraenoic and eicosapentaenoic acid [37] Essentialfatty acids are precursors of prostaglandins engenderingsignificant interest from the pharmaceutical industry
4 BioMed Research International
Table 2 Bioactive compounds extracted from Spirulina genus
23 Chlorella Spirulina and Chlorella represent the majorityof themicroalgal biomass market with an annual productionof 3000 and 4000 tons respectively [38] Chlorella sp isa eukaryotic genus of green unicellular microalgae thatbelongs to the Chlorophyta group (Figure 3) [39]
This microalga was discovered by the Japanese tradi-tional consumers of algae who usually enjoy it and use itas a food supplement The microalga Chlorella is rich inchlorophyll proteins polysaccharides vitamins mineralsand essential amino acids This microalga is 53 (ww)protein 23 (ww) carbohydrate 9 (ww) lipids and 5(ww) minerals and oligoelements [22]
These nutrient concentrations can be varied by manipu-lation of culture conditions The biomass of this microalga isalso rich in B complex vitamins especially B12 which arevital in the formation and regeneration of blood cells LikeSpirulina Chlorella has a GRAS certificate issued by the FDAand can thus be used as a food without risk to human healthwhen grown in a suitable environment with proper hygieneand good manufacturing practices [22 40]
Chlorella contains bioactive substances with medicinalproperties Experimental studies with Chlorella demon-strated their antitumor anticoagulant antibacterial antiox-idant and antihiperlipidemia effects in addition to a hepato-protective property and the immunostimulatory activity ofenzymatic protein hydrolyzate [39 41ndash44]
Many antioxidant compounds may be responsible forChlorella functional activities Antioxidants such as lutein 120572-carotene 120573-carotene ascorbic acid and 120572-tocopherol whichare active against free radicals were identified Some of thesecompounds not only are important as natural colorants oradditives but also may be useful in reducing the incidence ofcancer and in the prevention ofmacular degeneration [39 45](Table 4)
The most important bioactive compound in Chlorellais 120573-13 glucan an active immunostimulator that reducesfree radicals and blood cholesterol The efficacy of thiscompound against gastric ulcers sores and constipation hasbeen reported It also has been demonstrated to have preven-tive action against atherosclerosis and hypercholesterolemia
BioMed Research International 5
Table 4 Bioactive compounds extracted from the microalgae of the Chlorella genus
as well as antitumor activity [46] Chlorella is produced bymore than 70 companies Taiwan Chlorella ManufacturingCo (Taipei Taiwan) is the worldrsquos largest producer ofChlorella with over 400000 tons of biomass producedper year (httpwwwtaiwanchlorellacomindexphp) Sig-nificant production also occurs in Klotze (Germany) (80ndash100 t yrminus1 of dry biomass) [47]
24 Dunaliella Dunaliella is a green unicellular halotol-erant microalga that belongs to the Chlorophyceae group(Figure 4) This microalga is widely studied due to its tol-erance of extreme habitat conditions physiological aspectsand its many biotechnological applications Dunaliella is asource of carotenoids glycerol lipids and other bioactivecompounds such as enzymes and vitamins [48 49]
This microalga is a major source of natural 120573-caroteneable to produce up to 14 of its dry weight under conditionsof high salinity light and temperature as well as nutrientlimitation [50] In addition to 120573-carotene this microalgais rich in protein and essential fatty acids which can beconsumed safely as evidenced by GRAS recognition [22]Table 5 presents some compounds that have been extractedfrom microalgae of the Dunaliella genus
Compounds in the Dunaliella biomass have various bio-logical activities such as antioxidant antihypertensive bron-chodilatory analgesic muscle relaxant hepatoprotective andantiedemal properties The microalgal biomass can also be
used directly in food and pharmaceutical formulations [2251]
Chang et al [52] showed that Dunaliella cells containedantibiotic substances According to these authors the crudeextract of this microalga strongly inhibited the growthof Staphylococcus aureus Bacillus cereus Bacillus subtilisand Enterobacter aerogenes In another study Dunaliellamicroalga also showed antibacterial activity against variousmicroorganisms of importance to the food industry includ-ing Escherichia coli Staphylococcus aureus Candida albicansand Aspergillus niger [49 53]
Under ideal growing conditions Dunaliella can be stim-ulated to produce approximately 400mg of 120573-carotene persquare meter of growing area The cultivation of Dunaliellafor the production of 120573-carotene has been conducted inseveral countries including Australia Israel the USA andChina [54ndash56] An ingredient of Dunaliella with a strongability to stimulate cell proliferation and improve the energymetabolism of the skin was released by Pentapharm (BaselSwitzerland) [57] New pilot plants are under development inIndia Chile Mexico Cuba Iran Taiwan Japan Spain andKuwait [50]
3 Cultivation Conditions
The conditions for microalgal cultivation are important fac-tors that influence the metabolism of these microorganismsthus directing the synthesis of specific compounds of interestSeveral researchers have noted the influence of incubationtemperature the pH of themedium the period of cultivationaswell as salinity light intensity andmediumconstituents onthe synthesis of antimicrobial agents [58]
31 pH Temperature and Luminescence pH adjustments arethe primary measures used to prevent contamination bymicroorganisms such as other microalgae species pH con-trol is also essential for effective absorption of the compo-nents of the culture medium because it directly affects theavailability of various chemical elements [59] The reductionof some nutrients in the culturemedium can lead the produc-ing of specific biocompounds The difficulty of consuminga nitrogen source for example can lead microalgae to shiftyourmetabolism for lipids or carbohydrates production [60]
Light is an indispensable factor for photosynthesis caus-ing the cells to reproduce and thereby increasing the cell
6 BioMed Research International
Table 5 Bioactive compounds extracted from the microalgae of the Dunaliella genus
concentration [61] The illuminance also influences the bio-chemical composition of the biomass [62] The fatty acidcontent can be reducedwith increasing light incidenceThis isbecause lipids are the major components of chloroplasts andthe increased light energy demand greater activity of chloro-plasts [63] Studies also show the influence of illuminanceon the microalgae antioxidants According to Madhyastha[64] the application of blue light in the cultivation of themicroalga Spirulina fusiformis through a phenomenon wherethe microalgae cells alter the sequence of amino acids withcysteine repeats enhanced the antioxidant capacity
One of the most important factors for the growth of allliving organisms is the temperature The specific growth rateof the microalgae is directly correlated with the gross rate ofCO2
fixationO2
production (photosynthesis) and the respi-ration rate Photosynthesis and respiration are temperature-dependent with the respiration rate increasing exponentiallywith temperature [65] Temperature has a great influenceon the production of biomass proteins lipids and phenoliccompounds from microalgae The optimum temperature forcultivation of microalgae is 35ndash37∘C [66] In studies con-ducted by Noaman [58] that were performed to verifywhich culture conditions stimulated the greatest produc-tion of antimicrobial agents by the microalga Synechococcusleopoliensis it was observed that a temperature of 35∘C andpH 8 produced a maximum concentration of this bioactivecompound
32 Bioreactors Microalgae have attracted much interest forproduction of bioactive compounds and in order to growand tap the potentials of algae efficient photobioreactors arerequired A good number of photobioreactors can be used inproduction of various algal products [67] Innovative culti-vation systems andmodification of biochemical compositionof microalgae by simple changes in the growth media andcultivation conditions (nutrients light intensity temperaturepH mixing etc) can lead to higher productivity of thetargeted products [68]
Bioreactors can be classified as open or closed Closedphotobioreactors have attracted much interest because theyallow a better control of the cultivation conditions than opensystems One of the major advantages of open ponds is thatthey are easier to construct and operate than most closedsystems [67]
In open systems temperature is a main limiting factoras are variations in solar radiation that lead to low biomassconcentrations However open systems are the most widely
used due to their economic viability Closed systems aregenerally used on a pilot scale for investigating problemsrelated to economic viability Furthermore the use of closedsystems is primarily used for microalgal species that do notgrow in a highly selective medium avoiding contaminationof the cultures [69]
Closed bioreactors can provide high productivity gen-erating greater microalgal biomass per unit time Otheradvantages of the use of closed bioreactors compared withopen systems include the following (i) virtually zero losses inconnection with evaporation (ii) a marked reduction ofproblems related to culture contamination by heterotrophicalgae or othermicroorganisms (iii) ease of biomass collectionprocedures due to smaller volumes of culture medium (iv)greater control of gas exchange between the culture andthe atmosphere (v) a smaller occupied space (vi) a highsurfacevolume ratio which helps to increase the illuminationof the system and (vii) the possibility of obtaining high puritycultures [59]
33 Nutrients The metabolism of microalgae can beautotrophic or heterotrophic The former requires onlyinorganic compounds such as CO
2
salts and solar energythe latter is not photosynthetic requiring an external sourceof organic compounds for use as a nutrient and energy sourceSome photosynthetic species are mixotrophic having theability to perform photosynthesis and use exogenous organicsources simultaneously [70]
Microalgae react to changes in their external environmentwith changes in their intracellular environment Thus themanipulation of the culture conditions or the presence orabsence of nutrients stimulates the biosynthesis of specificcompounds This fact was first referenced by Richmond[71] who changed the composition of Chlorella biomassparticularly in their protein and lipid content by varyingcultivation conditions
Noaman [58] found that leucine combined with citrateor acetate is the sources of nitrogen and carbon that pro-duced higher concentrations of antimicrobial agents in themicroalga Synechococcus leopoliensis Coca et al [72] study-ing the cultivation of Spirulina platensis in a medium sup-plemented with vinasse obtained an increased protein yieldcompared to the unsupplemented culture medium Ip andChen [73] studying the cultivation of Chlorella zofingiensisunder mixotrophic cultivation conditions found that lowconcentrations of nitrate and a high glucose concentrationfavored the production of astaxanthin in this microalga
BioMed Research International 7
Alonso et al [74] studying the influence of nitrogen con-centration in continuous cultivation on lipid concentrationin Phaeodactylum tricornutum noted that there was accu-mulation of saturated and unsaturated fatty acids when thenitrogen source was reduced
Culture media are chemical preparations that are formu-lated to contain the nutrients necessary for the microorgan-isms to multiply andor survive The culture media shouldmeet the nutritional needs of the microorganism assist inprocess control and have a reasonably fixed composition[75]
Among different microalgae variations in the culturemedium are mainly related to the amount of necessary nutri-ents Even so nutritional needs are dependent on environ-mental conditions [59] Microalgae require macronutrientssuch as C N O H P Ca Mg S and K for their growthThe micronutrients that are generally required are Fe MnCu Mo and Co Additionally some species require lowerconcentrations of vitamins in the culture medium [76]
4 Advantages of Using Microalgae to ObtainBioactive Compounds
Microalgae are important sources of bioactive natural sub-stances Many metabolites isolated from these microorgan-isms have shown biological activities and potential healthbenefits [77] Microalgae accumulate specific secondarymetabolites (such as pigments and vitamins) which are highvalue products that have applications in the cosmetic foodor pharmaceutical industries [8 78]
Microalgae live in complex habitats and are subjectedto stress andor extreme conditions such as changes insalinity temperature and nutrients Thus these microorgan-isms must rapidly adapt to new environmental conditions tosurvive and thus produce a great variety of biologically activesecondary metabolites that are not found in other organisms[79] Some of the advantages of microalgal cultivation maybe associated with taxonomic diversity the diverse chemicalcomposition the potential for growth in a bioreactor undercontrolled conditions and the ability to produce activesecondary metabolites in response to the stress induced byextreme exposure conditions [39 80]
In addition to their natural characteristics other impor-tant aspects related to microalgae are the use of solar energyand carbon dioxide (CO
2
) and a high growth rate whichcan produce higher yields compared to higher plants Inaddition microalgae can be grown in areas and climates thatare unsuitable for agriculture therefore microalgae do notcompete with arable food production land The possibility ofcontrolling the production of certain bioactive compoundsby manipulation of culture conditions is another advantageof using microalgae [7 81ndash83]
The cultivation of microalgae is a major mechanism forreducing excess carbon dioxide (CO
2
) in the atmosphere bybiofixation in which an industrial process uses a CO
2
-richgas as a carbon source formicroalgal growthThismechanismcontributes to a reduction of the greenhouse effect and globalwarming further reducing the costs of the carbon source
for growth which is the greatest nutrient requirement formicroalgae [13 84]
The cultivation of microalgae is not seasonal they areimportant for food in aquaculture systems and can effectivelyremove pollutants such as nitrogen and phosphorus fromwastewater Moreover they are themost efficient solar energybiomass converters Microalgae cultivation via sunlight-dependent systems contributes to sustainable developmentand natural resource management [13]
The integration of the production process of bioactivemetabolites in a biorefinery is a sustainable means of energyproduction food production and the production of productswith high added value [7] The biorefinery concept based onmicroalgae depends on the efficient use of biomass throughfractionation resulting in several isolated productsThis con-cept encompasses a biorefinery platform which is capable ofoffering a wide variety of different products such as productswith applications in pharmaceuticals medicine food (pro-tein fiber) and biofuels [7 85] These benefits contribute tothe economic viability of microalgal production [7 8]
5 Bioactive Compounds
Bioactive compounds are physiologically active substanceswith functional properties in the human body There is greatenthusiasm for the development and manufacture of variousbiocompounds that can potentially be used as functionalingredients such as carotenoids phycocyanins polyphenolsfatty acids and polyunsaturated compounds [16]
An interest in the production of bioactive compoundsfrom natural sources has recently emerged driven by agrowing number of scientific studies that demonstrate thebeneficial effects of these compounds on health [80] Naturalproducts are important in the search for new pharmaco-logically active compounds In general they play a role indrug discovery for the treatment of human diseases [86]Many clinically viable and commercially available drugs withantitumor and antiinfective activity originated as naturalproducts
Microalgae are a natural source of interesting biocom-pounds Microalgae are known to produce various therapeu-tically effective biocompounds that can be obtained from thebiomass or released extracellularly into the medium [11]These microorganisms contain many bioactive compoundssuch as proteins polysaccharides lipids vitamins enzymessterols and other high-value compounds with pharmaceu-tical and nutritional importance that can be employed forcommercial use [13]
51 Compounds with Antioxidant Function Oxidative dam-age caused by reactive oxygen species to lipids proteins andnucleic acids can cause many chronic diseases such as heartdisease atherosclerosis cancer and aging Epidemiologicalstudies have demonstrated an inverse association between theintake of fruits and vegetables and mortality from diseasessuch as cancer This phenomenon can be attributed to theantioxidant activity of these foods [87]
8 BioMed Research International
Microalgal biomass is considered a rich natural source ofantioxidants with potential applications in food cosmet-ics and medicine [87] Antioxidant compounds such asdimethylsulfoniopropionate and mycosporine amino acidswere isolated frommicroalgae and are potent chemical block-ers ofUV radiation [88] In addition to these compounds pig-ments lipids and polysaccharides with antioxidant activitycan also be found in microalgal biomass
Carotenoids and phycocyanins are the pigments mostused in scientific research C-phycocyanin (C-PC) is a bluephotosynthetic pigment that belongs to the group of phyco-biliproteins found in large quantities in the cyanobacteriaRhodophyta and Cryptophyte [89] Phycocyanin has appli-cations as a nutrient and natural food colorants and cosmet-ics It is usually extracted from the biomass of Spirulina [90]and Porphyridium cruentum [91] and Synechococcus [89]
Among the carotenoid compounds 120573-carotene andastaxanthin are prominent These compounds have appli-cation in the food and pharmaceutical industries becauseof their antioxidant properties and pigmentation ability Inmicroalgal metabolism they protect photosynthetic tissuesagainst damage caused by light and oxygen [92] Dunaliellasalina is a microalga recognized as a major biological sourceof 120573-carotene pigment producing more than 14 in drybiomass [46] H pluvialis is a source of the pigment astax-anthin producing 1ndash8 of astaxanthin as dry biomass [93]
Polysaccharides represent a class of high value-addedcomponents with applications in food cosmetics fabrics sta-bilizers emulsifiers and medicine [94] Microalgal polysac-charides contain sulphate esters are referred to as sulfatedpolysaccharides and possess unique medical applicationsThe basic mechanism of therapeutic action is based on thestimulation of macrophages and modulation The biologicalactivity of sulfur polysaccharides is linked to their sugarcomposition position and degree of sulfation [95] Amongthe microalgae capable of producing these compounds areChlorella vulgaris Scenedesmus quadricauda [96] and Por-phyridium sp [97]
52 Compounds with Antimicrobial Activity The importanceof discovering new compounds with antimicrobial activityis driven by the development of antibiotic resistance inhumans due to constant clinical use of antibioticsMicroalgaeare an important source of antibiotics with a broad andefficient antibacterial activity [11] The antimicrobial activityof these microorganisms is due to the ability to synthesizecompounds such as fatty acids acrylic acids halogenatedaliphatic compounds terpenoids sterols sulfur-containingheterocyclic compounds carbohydrates acetogenins andphenols [98]
The antimicrobial activity of extracts from microalgae isrelated to its lipid composition The antimicrobial action ofmicroalgae is also noteworthy because of the potential toproduce compounds such as 120572- and 120573-ionone 120573-cyclocitralneophytadiene and phytol [99] Microalgae antimicrobialactivity against human pathogens such as Escherichia coliPseudomonas aeruginosa Staphylococcus aureus and Staphy-lococcus epidermidis has been attributed to 120574-linolenic acid
The mechanism of action of fatty acids affects variousstructures in microorganisms however cell membranes arethe most impacted Membrane damage most likely leadsto a loss of internal substances from the cells and theentry of harmful components reduces nutrient absorption inaddition to inhibiting cellular respiration The ability of fattyacids to interfere with bacterial growth depends on boththeir chain length and the degree of unsaturation Fatty acidswith more than 10 carbon atoms apparently induce lysis ofbacterial protoplasts [99]
Microbial polysaccharides and other biological com-pounds have antiviral and antimicrobial action Microalgaeproduce extracellular sulfated polysaccharide (EPS) withacidic characteristics that has a potential as a therapeuticagent [101] Highly sulfated antiviral polysaccharides fromseveral species of microalgae consist mainly of xylose glu-cose and galactose The EPS sulfate groups determine somecharacteristics of polysaccharides it has been found thathigher sulphate contents induced higher antiviral activities[94 101] The inhibitory effect of polysaccharides of microal-gal origin is due to viral interactions or positive charges onthe cell surface thereby preventing penetration of the virusinto host cells [99]
The cyanobacterium Spirulina (Arthrospira) can producesulfated polysaccharides that have already found applicationsas antiviral agents both in vivo and in vitro [102] Eukaryoticmicroalgae such as Chlorella sp and Dunaliella sp produceand secrete polysaccharides at relatively high levels [17] Theantibacterial ability of Spirulina has been correlated withtheir volatile composition resulting in the identification of15 elements which constitutes 96 of total compounds Themajor volatile components produced by Spirulina consist ofheptadecane (40) and tetradecane (35) [39]
Some studies have reported that sulfated polysaccharidesderived from microalgae inhibit viral infection such asencephalomyocarditis virus Herpes simplex virus types 1and 2 (HSV1 HSV2) human immunodeficiency virus (HIV)hemorrhagic septicemia in salmonid virus swine fever virusand varicella virus [99 103] Carrageenan is a sulfatedpolysaccharide that can directly bind to human papillo-mavirus to inhibit not only the viral adsorption process butalso the input and subsequent process of the uncoating of thevirus [101]
53 Compounds with Anti-Inflammatory Action Inflam-mation is an immediate reaction to a cell or tissueinjury caused by noxious stimuli such as toxins andpathogens In this situation the body recognizes theagents responsible for the attack and attempts to neu-tralize them as quickly as possible Inflammation causesredness swelling heat and pain usually located at thesite of infection [104] Ingestion of anti-inflammatory com-pounds enhances the bodyrsquos immune response and helpsto prevent disease and aids the healing process Microal-gae produce several anti-inflammatory compounds in their
BioMed Research International 9
biomass that may exert a protective function in the bodywhen consumed as food or used as pharmaceuticals andcosmetics
Because of its anti-inflammatory capabilities microalgalbiomass is being considered for applications in tissue engi-neering for the development of scaffolds for use in reconsti-tution of organs and tissues [105 106] This is an importantapplication for humans especially in patients with burnsin which the skin was completely lost [107] Among themost important microalgal compounds with such prop-erties are long-chain polyunsaturated fatty acids (PUFAs)[108 109] sulfurized polysaccharides [110] and pigments[111]
Many microalgal polysaccharides possess the ability tomodulate the immune system through the activation ofmacrophage functions and the induction of reactive oxy-gen species (ROS) nitric oxide (NO) and various othertypes of cytokineschemokines [112] Macrophages are ableto regulate several innate responses and secrete cytokinesand chemocytokines that serve as signals for immune andinflammatory molecular reactions [113] Sulfur polysaccha-rides with anti-inflammatory activity can be applied inskin treatments inhibiting the migration and adhesion ofpolymorphonuclear leukocytes [110] Guzman et al [114]studied the anti-inflammatory capacity of the microalgaChlorella stigmatophora and Phaeodactylum tricomutum andconcluded that bothmicroalgae showed positive responses inthe test of paw edema by carrageenan
The PUFAs especially 1205963 and 1205966 as eicosapentaenoic(EPA) docosahexaenoic (DHA) and arachidonic (AA) acidshave been applied in the treatment of chronic inflammationsuch as rheumatism and skin diseases [108] Ryckebosch etal [115] evaluated the nutritional value of the total lipidsextracted from different PUFAs produced by microalgae Inthis study the microalgae IsochrysisNannochloropsis Phaeo-dactylum Pavlova and Thalassiosira produced 1205963 PUFA asan alternative to fish oil in food
Among the pigments with anti-inflammatory activityfucoxanthin carotenoid found in diatoms [116 117] is capableof stimulating apoptosis in human cancer cells [118] A phy-cocyanin found in cyanobacteria has an anti-inflammatoryactivity that occurs through the inhibition of histaminerelease [111 119]
54 Compounds with Potentiality over Degenerative Dis-eases In humans the oxidation reactions driven by reactiveoxygen species (ROS) can lead to irreversible damage tocellular components including lipids proteins and DNAdegradation andor mutation Consequently this damagecan lead to several syndromes such as cardiovascular dis-ease some cancers and the degenerative diseases of aging[120]
Chronic age-related diseases involve oxidative stress andinflammation and their consequences Chronic inflammationplays a significant role in the mediation of neurodegenerativediseases such as Parkinsonrsquos disease Alzheimerrsquos diseasemultiple sclerosis acquired immunodeficiency syndrome(AIDS) and dementia complex [77]
Natural pigments derived from microalgae (NPs) haveneuroprotective properties being valuable sources as func-tional ingredients in foods and pharmaceutical products thatshow efficient action in the treatment andor prevention ofneurodegenerative diseases Vitamin E has preventive effectsfor many diseases such as atherosclerosis and heart diseaseas well as neurodegenerative diseases such as multiplesclerosis [77]
Carotenoids have great potential benefits to humanhealth including the treatment of degenerative diseases suchas macular degeneration and cataract development Thesecompounds act as antioxidants reducing oxidative damageby ROS Studies indicated that increased intake of phenolsdecreased the occurrence of degenerative diseases Phenoliccompounds from microalgae with the potential to fight freeradicals have been reported [121]
Dunaliella salina is a natural source of 120573-carotene whichproduced a reduced risk of cancer and degenerative diseasesin humans Lutein is effective against various diseases includ-ing cataracts and macular degeneration and in the earlystages of atherosclerosis Extracts of Chlorella sp containing120573-carotene and lutein significantly prevented the cognitivedisability that accompanies Alzheimerrsquos disease in rats It wasalso reported that lutein extracted from Chlorella reducedthe incidence of cancer Likewise carotenoids extractedfrom Chlorella ellipsoidea and Chlorella vulgaris inhibited thegrowth of colon cancer [122] A lycopene extracted fromthe microalgae Chlorella marina significantly reduced theproliferation of prostate cancer inmice [123]This compoundalso reduced total cholesterol and low-density lipoprotein(LDL) levels [123] and improved rheumatoid arthritis [124]
Low plasma levels of lutein have also been associatedwith an increased tendency ofmyocardial infarction whereashigh intake of lutein was related to a decreased risk ofstroke In addition high levels of carotenoids with provi-tamin A activity including 120572-carotene 120573-carotene and 120573-cryptoxanthin have been associated with reduction in therisk of angina pectoris Macular degeneration the lead-ing cause of irreversible vision loss has also been associ-ated with very low consumption of lutein and zeaxanthin[125]
Scientific findings indicate astaxanthin for multimodalintervention formany forms of degenerative diseases includ-ing cardiovascular diseases cancer metabolic syndromecognitive impairment age-related immune dysfunctionstomach and ocular diseases (macular degeneration cataractglaucoma diabetic retinopathy and retinitis pigmentosa)and skin damage [126] High levels of lycopene in plasmaand tissues were inversely related to coronary heart diseasemyocardial infarction and the risk of atherosclerosis [125]
55 Compounds withHealth Promoting Function The impor-tance of microalgae as sources of functional ingredients hasbeen recognized because of their beneficial health effectsNatural pigments are valuable sources of bioactive com-pounds These pigments have various beneficial biologicalactivities such as antioxidant anticancer anti-inflammatoryantiobesity antiangiogenic and neuroprotective action and
10 BioMed Research International
are indicated for the treatment or prevention of severalchronic diseases [77]
The antioxidant potential of carotenoid pigments andtheir ability to prevent cancer aging atherosclerosis coro-nary heart disease and degenerative diseases have beendescribed 120573-Carotene has higher provitamin A activitywhich is essential for vision and the correct functioning ofthe immune system Astaxanthin is linked to many healthbenefits such as protection against lipid peroxidation age-related macular degeneration reduced atherosclerosis andan increased immune response [102]
Fucoxanthin is considered as a promising dietary andweight loss supplement and for the treatment of obesityClinical studies by Abidov et al [127] demonstrated the effectof ldquoxanthigenrdquo a fucoxanthin based antiobesity supplementFurthermore fucoxanthinmay be useful for the prevention ofbone diseases such as osteoporosis and rheumatoid arthritisIt has also been reported to be effective for the therapeutictreatment of diabetic diseases suppressing insulin and hyper-glycemia [77]
Microalgae proteins are of great interest as a source ofbioactive peptides due to their therapeutic potential in thetreatment of various diseases [7] Proteins peptides andamino acids have functions that contribute to health benefitsThese compounds can include growth factors hormones andimmunomodulators and can help to replace damaged tissuesin addition to providing nutritional benefits Microalgaesuch as Chlorella and Spirulina (Arthrospira) may be usedas nutraceuticals or included in functional foods to preventdiseases and damage to cells and tissues due to their richprotein content and amino acid profile [102]
The antimicrobial action of certain enzymes (eglysozyme) and immunoglobulins has been reported andrecommended for people with different diseases (egCrohnrsquos disease) due to the existence of formulations withpeptides and free amino acids Studies of the healtheffects of lysozyme have been reported in the microalgaeSpirulina platensis [128] Chlorella [129] and Dunaliellasalina [130] Spirulina (Arthrospira) and Chlorella biomasspills are marketed as is ldquoHawaiian Spirulina Pacificardquo(httpspirulinagreennutritionalscomau) Other proteinscan also increase the production of cholecystokinin involvedin appetite suppression and the reduction of LDL-cholesterolProtein peptides from Chlorella have a potential as dietarysupplements for the prevention of oxidative stress-relateddiseases such as atherosclerosis coronary heart disease andcancer [39]
The essential fatty acids 120596-3 and 120596-6 in particular areimportant for the integrity of tissues 120574-Linolenic acid hastherapeutic applications in cosmetics to revitalize the skinand thus slow aging Linoleic and linolenic acids are essentialnutrients for the immune system and other related tissueregeneration processes Linoleic acid is also used for thetreatment of hyperplasia of the skin [102]
The most studied microalgal lipid compounds are thepolyunsaturated fatty acids (PUFAs) docosahexaenoic acid(120596-3 C226) (DHA) eicosapentaenoic acid (C20 120596-35)(EPA) and arachidonic acid (120596-6 C204) (ARA) Studies haveshown that dietary120596-3 PUFAs have a protective effect against
atherosclerotic heart disease [131] DHA and EPA showed theability to reduce problems associated with strokes and arthri-tis besides reducing hypertension lipid content (a decreasein triglycerides and an increase of HDL) and acting asanti-inflammatory agents DHA is also important in thedevelopment and function of the nervous system Further-more ARA and EPA are platelet aggregators vasoconstric-tors and vasodilators and have antiaggregative action on theendothelium as well as chemostatic activity in neutrophils[102]
Other lipid compounds with interesting bioactive prop-erties are the microalgal sterols Phytosterols have demon-strated reduction of total cholesterol (LDL) in humans byinhibiting its absorption from the intestine [50] Polysac-charides can be considered as dietary fibers associatedwith different physiological effects Insoluble fiber (cellulosehemicellulose and lignin) mainly promotes the movementof material through the digestive system thereby improvinglaxation and increasing satietyThey can also be considered asprebiotics because they promote the growth of gutmicrofloraincluding probiotic species Soluble fiber (oligosaccharidespectins and 120573-glucans) may reduce cholesterol and regulateblood glucose [7 132]
6 Conclusion
The proven ability of microalgae to produce bioactive com-pounds places these microorganisms in the biotechnologicalspotlight for applications in various areas of study especiallyin the life sciencesThe production ofmicroalgal metaboliteswhich stimulate defense mechanisms in the human bodyhas spurred intense study of the application of microalgalbiomass in various foods and pharmacological and medicalproducts There is obviously a need for further study of theidentified compounds and their activities in the treatmentand prevention of various diseases in addition to an ongoingsearch for other as yet undetected metabolites
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgment
The authors thank the National Counsel of Technologicaland Scientific Development (CNPq) for the Productivityin Technological Development and Innovative ExtensionScholarship
References
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[2] A A El Gamal ldquoBiological importance of marine algaerdquo SaudiPharmaceutical Journal vol 18 no 1 pp 1ndash25 2010
BioMed Research International 11
[3] I Moreno-Garrido ldquoMicroalgae immobilization current tech-niques and usesrdquo Bioresource Technology vol 99 no 10 pp3949ndash3964 2008
[4] R-B Volk and F H Furkert ldquoAntialgal antibacterial andantifungal activity of two metabolites produced and excretedby cyanobacteria during growthrdquoMicrobiological Research vol161 no 2 pp 180ndash186 2006
[5] R-B Volk ldquoA newly developed assay for the quantitativedetermination of antimicrobial (anticyanobacterial) activity ofboth hydrophilic and lipophilic test compounds without anyrestrictionrdquoMicrobiological Research vol 163 no 2 pp 161ndash1672008
[6] D F Smee K W Bailey M-H Wong et al ldquoTreatment ofinfluenza A (H1N1) virus infections in mice and ferrets withcyanovirin-Nrdquo Antiviral Research vol 80 no 3 pp 266ndash2712008
[7] E Ibanez and A Cifuentes ldquoBenefits of using algae as naturalsources of functional ingredientsrdquo Journal of the Science of Foodand Agriculture vol 93 no 4 pp 703ndash709 2013
[8] G Markou and E Nerantzis ldquoMicroalgae for high-valuecompounds and biofuels production a review with focus oncultivation under stress conditionsrdquo Biotechnology Advancesvol 31 no 8 pp 1532ndash1542 2013
[9] R Harun M Singh G M Forde andM K Danquah ldquoBiopro-cess engineering ofmicroalgae to produce a variety of consumerproductsrdquo Renewable and Sustainable Energy Reviews vol 14no 3 pp 1037ndash1047 2010
[10] C Kolympiris N Kalaitzandonakes and D Miller ldquoPublicfunds and local biotechnology firm creationrdquo Research Policyvol 43 no 1 pp 121ndash137 2014
[11] S Bhagavathy P Sumathi and I Jancy Sherene Bell ldquoGreenalgae Chlorococcum humicola-a new source of bioactive com-pounds with antimicrobial activityrdquo Asian Pacific Journal ofTropical Biomedicine vol 1 no 1 pp S1ndashS7 2011
[12] A M F Palavra J P Coelho J G Barroso et al ldquoSupercrit-ical carbon dioxide extraction of bioactive compounds frommicroalgae and volatile oils from aromatic plantsrdquo Journal ofSupercritical Fluids vol 60 pp 21ndash27 2011
[13] I Priyadarshani and B Rath ldquoCommercial and industrialapplications of micro algaemdasha reviewrdquo Journal of Algal BiomassUtilization vol 3 no 4 pp 89ndash100 2012
[14] JW Blunt B R CoppM H GMunro P T Northcote andMR Prinsep ldquoMarine natural productsrdquoNatural Product Reportsvol 23 no 1 pp 26ndash78 2006
[15] A M S Mayer and M T Hamann ldquoMarine pharmacologyin 2001-2002 marine compounds with anthelmintic antibacte-rial anticoagulant antidiabetic antifungal anti-inflammatoryantimalarial antiplatelet antiprotozoal antituberculosis andantiviral activities affecting the cardiovascular immune andnervous systems and other miscellaneous mechanisms ofactionrdquo Comparative Biochemistry and Physiology Part C Toxi-cology amp Pharmacology vol 140 no 3-4 pp 265ndash286 2005
[16] M Plaza S Santoyo L Jaime et al ldquoScreening for bioactivecompounds from algaerdquo Journal of Pharmaceutical and Biomed-ical Analysis vol 51 no 2 pp 450ndash455 2010
[17] I Rodrıguez-Meizoso L Jaime S Santoyo et al ldquoPressurizedfluid extraction of bioactive compounds from Phormidiumspeciesrdquo Journal of Agricultural and Food Chemistry vol 56 no10 pp 3517ndash3523 2008
[18] L R Carvalho A Costa-Neves G A A Conserva et alldquoBiologically active compounds from cyano bacteria extracts in
vivo and in vitro aspectsrdquo Brazilian Journal of Pharmacognosyvol 23 no 3 pp 471ndash480 2013
[19] B Nobre FMarcelo R Passos et al ldquoSupercritical carbon diox-ide extraction of astaxanthin and other carotenoids from themicroalga Haematococcus pluvialisrdquo European Food Researchand Technology vol 223 no 6 pp 787ndash790 2006
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extraction of 120574-linolenic acid and other lipids from Arthrospira(Spirulina)maxima comparison with organic solvent extrac-tionrdquo Food Chemistry vol 99 no 1 pp 57ndash63 2006
[21] I Romano M R Bellitti B Nicolaus et al ldquoLipid profilea useful chemotaxonomic marker for classification of a newcyanobacterium in Spirulina genusrdquo Phytochemistry vol 54 no3 pp 289ndash294 2000
[22] J A C Costa and M G Morais ldquoMicroalgae for food produc-tionrdquo in Fermentation Process Engineering in the Food IndustryC R Soccol A Pandey and C Larroche Eds p 486 Taylor ampFrancis 2013
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[25] F S Antelo J A V Costa and S J Kalil ldquoThermal degradationkinetics of the phycocyanin from Spirulina platensisrdquo Biochem-ical Engineering Journal vol 41 no 1 pp 43ndash47 2008
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[79] I Rodrıguez-Meizoso L Jaime S Santoyo F J Senorans ACifuentes and E Ibanez ldquoSubcritical water extraction andcharacterization of bioactive compounds from Haematococcuspluvialis microalgardquo Journal of Pharmaceutical and BiomedicalAnalysis vol 51 no 2 pp 456ndash463 2010
[80] M Herrero M Castro-Puyana J A Mendiola and E IbanezldquoCompressed fluids for the extraction of bioactive compoundsrdquoTrends in Analytical Chemistry vol 43 pp 67ndash83 2013
[81] N K Singh and D W Dhar ldquoMicroalgae as second generationbiofuel A reviewrdquo Agronomy for Sustainable Development vol31 no 4 pp 605ndash629 2011
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production of bioactive compounds from Tetraselmis suecica atpilot scalerdquo Journal of Cleaner Production vol 64 pp 323ndash3312014
[85] B Subhadra ldquoAlgal biorefinery-based industry an approachto address fuel and food insecurity for a carbon-smart worldrdquoJournal of the Science of Food and Agriculture vol 91 no 1 pp2ndash13 2011
[86] D J Newman and G M Cragg ldquoNatural products as sourcesof new drugs over the 30 years from 1981 to 2010rdquo Journal ofNatural Products vol 75 no 3 pp 311ndash335 2012
[87] H-B Li K-W Cheng C-C Wong K-W Fan F Chen andY Jiang ldquoEvaluation of antioxidant capacity and total phenoliccontent of different fractions of selected microalgaerdquo FoodChemistry vol 102 no 3 pp 771ndash776 2007
[88] T M Mata A A Martins and N S Caetano ldquoMicroalgaefor biodiesel production and other applications a reviewrdquoRenewable and Sustainable EnergyReviews vol 14 no 1 pp 217ndash232 2010
[89] A Gupta and J K Sainis ldquoIsolation of C-phycocyanin fromSynechococcus sp (Anacystis nidulans BD1)rdquo Journal of AppliedPhycology vol 22 no 3 pp 231ndash233 2010
[90] P J Viskari and C L Colyer ldquoRapid extraction of phyco-biliproteins from cultured cyanobacteria samplesrdquo AnalyticalBiochemistry vol 319 no 2 pp 263ndash271 2003
[91] R Bermejo Roman J M Alvarez-Pez F G Acien Fernandezand E Molina Grima ldquoRecovery of pure B-phycoerythrin fromthe microalga Porphyridium cruentumrdquo Journal of Biotechnol-ogy vol 93 no 1 pp 73ndash85 2002
[92] C I Cazzonelli ldquoCarotenoids in nature insights from plantsand beyondrdquo Functional Plant Biology vol 38 no 11 pp 833ndash847 2011
[93] M A Hejazi and R HWijffels ldquoMilking of microalgaerdquo Trendsin Biotechnology vol 22 no 4 pp 189ndash194 2004
[94] S Arad and O Levy-Ontman ldquoRed microalgal cell-wallpolysaccharides biotechnological aspectsrdquo Current Opinion inBiotechnology vol 21 no 3 pp 358ndash364 2010
[95] M Kim J H Yim S-Y Kim et al ldquoIn vitro inhibitionof influenza A virus infection by marine microalga-derivedsulfated polysaccharide p-KG03rdquoAntiviral Research vol 93 no2 pp 253ndash259 2012
[96] Z A Mohamed ldquoPolysaccharides as a protective responseagainst microcystin-induced oxidative stress in Chlorella vul-garis and Scenedesmus quadricauda and their possible signifi-cance in the aquatic ecosystemrdquo Ecotoxicology vol 17 no 6 pp504ndash516 2008
[97] T Tannin-Spitz M Bergman D Van-Moppes S Grossmanand S Arad ldquoAntioxidant activity of the polysaccharide of thered microalga Porphyridium sprdquo Journal of Applied Phycologyvol 17 no 3 pp 215ndash222 2005
[98] J W Prakash M Johnson and S Jeeva ldquoAntimicrobial activityof certain fresh water microalgae from Thamirabarani RiverTamil Nadu South Indiardquo Asian Pacific Journal of TropicalBiomedicine vol 1 supplement no 2 pp S170ndashS173 2011
[99] H M Amaro A C Guedes and F X Malcata ldquoAntimicrobialactivities of microalgae an invited reviewrdquo in Science againstMicrobial Pathogens Communicating Current Research andTechnological Advances A Mendez-Vilas Ed pp 1272ndash12802011
[100] V J Smith A PDesbois and E ADyrynda ldquoConventional andunconventional antimicrobials from fish marine invertebratesand micro-algaerdquo Marine Drugs vol 8 no 4 pp 1213ndash12622010
14 BioMed Research International
[101] M F D J Raposo A M M B de Morais and R M SC de Morais ldquoInfluence of sulphate on the composition andantibacterial and antiviral properties of the exopolysaccharidefrom Porphyridium cruentumrdquo Life Sciences vol 101 no 1-2 pp56ndash63 2014
[102] M F De Jesus Raposo R M S C De Morais and A M M BDe Morais ldquoHealth applications of bioactive compounds frommarine microalgaerdquo Life Sciences vol 93 no 15 pp 479ndash4862013
[103] A Smelcerovic Z Knezevic-Jugovic and Z PetronijevicldquoMicrobial polysaccharides and their derivatives as current andprospective pharmaceuticalsrdquo Current Pharmaceutical Designvol 14 no 29 pp 3168ndash3195 2008
[104] M T Madigan J M Martinko P V Dunlap and D P ClarkMicrobiologia de Brock Artmed Editora 12th edition 2010
[105] M G de Morais J A V Costa P H L Pranke et alldquoDevelopment of a newnanofiber scaffold for usewith stemcellsin a third degree burn animal modelrdquo Burns Oxford vol 40 no8 pp 1650ndash1660 2014
[106] M G de Morais C Stillings R Dersch et al ldquoPreparation ofnanofibers containing the microalga Spirulina (Arthrospira)rdquoBioresource Technology vol 101 no 8 pp 2872ndash2876 2010
[107] D Steffens M Lersch A Rosa et al ldquoA new biomaterialof nanofibers with the microalga Spirulina as scaffolds tocultivate with stem cells for use in tissue engineeringrdquo Journalof Biomedical Nanotechnology vol 9 no 4 pp 710ndash718 2013
[108] C Barrow and F ShahidiMarine Nutraceuticals and FunctionalFoods CRC Press Taylor amp Francis Boca Raton Fla USA2008
[109] M N A Khan J-Y ChoM-C Lee et al ldquoIsolation of two anti-inflammatory and one pro-inflammatory polyunsaturated fattyacids from the brown seaweed Undaria pinnatifidardquo Journal ofAgricultural and Food Chemistry vol 55 no 17 pp 6984ndash69882007
[110] M S Matsui N Muizzuddin S Arad and K MarenusldquoSulfated polysaccharides from redmicroalgae have antiinflam-matory properties in vitro and in vivordquo Applied Biochemistryand Biotechnology vol 104 no 1 pp 13ndash22 2003
[111] V B Bhat and K M Madyastha ldquoScavenging of peroxynitriteby phycocyanin and phycocyanobilin from Spirulina platensisprotection against oxidative damage to DNArdquo Biochemical andBiophysical Research Communications vol 285 no 2 pp 262ndash266 2001
[112] I A Schepetkin and M T Quinn ldquoBotanical polysaccharidesmacrophage immunomodulation and therapeutic potentialrdquoInternational Immunopharmacology vol 6 no 3 pp 317ndash3332006
[113] J K Park Z-H Kim C G Lee et al ldquoCharacterization andimmunostimulating activity of a water-soluble polysaccharideisolated from Haematococcus lacustrisrdquo Biotechnology and Bio-process Engineering vol 16 no 6 pp 1090ndash1098 2011
[114] S Guzman A Gato M Lamela M Freire-Garabal and J MCalleja ldquoAnti-inflammatory and immunomodulatory activitiesof polysaccharide from Chlorella stigmatophora and Phaeo-dactylum tricornutumrdquo Phytotherapy Research vol 17 no 6 pp665ndash670 2003
[115] E Ryckebosch C Bruneel R Termote-Verhalle K Goiris KMuylaert and I Foubert ldquoNutritional evaluation of microalgaeoils rich in omega-3 long chain polyunsaturated fatty acids as analternative for fish oilrdquo Food Chemistry vol 160 pp 393ndash4002014
[116] P Zhao Z Zang X Xie A Huang and G Wang ldquoTheinfluence of different flocculants on the physiological activityand fucoxanthin production of Phaeodactylum tricornutumrdquoProcess Biochemistry vol 49 no 4 pp 681ndash687 2014
[117] D Moreau C Tomasoni C Jacquot et al ldquoCultivated microal-gae and the carotenoid fucoxanthin from Odontella auritaas potent anti-proliferative agents in bronchopulmonary andepithelial cell linesrdquo Environmental Toxicology and Pharmacol-ogy vol 22 no 1 pp 97ndash103 2006
[118] H Maeda M Hosokawa T Sashima K Funayama and KMiyashita ldquoFucoxanthin from edible seaweed Undaria pinnati-fida shows antiobesity effect through UCP1 expression in whiteadipose tissuesrdquo Biochemical and Biophysical Research Commu-nications vol 332 no 2 pp 392ndash397 2005
[119] J E Piero Estrada P Bermejo Bescos and A M Villar delFresno ldquoAntioxidant activity of different fractions of Spirulinaplatensis protean extractrdquo IL Farmaco vol 56 no 5ndash7 pp 497ndash500 2001
[120] S-M Kang S-J Heo K-N Kim S-H Lee and Y-JJeon ldquoIsolation and identification of new compound 2710158401015840-phloroglucinol-661015840-bieckol from brown algae Ecklonia cavaand its antioxidant effectrdquo Journal of Functional Foods vol 4no 1 pp 158ndash166 2012
[121] HHAbdEl-Baky F K El Baz andG S El-Baroty ldquoProductionof phenolic compounds from Spirulinamaximamicroalgae andits protective effectsrdquoAfrican Journal of Biotechnology vol 8 no24 pp 7059ndash7067 2009
[122] A C Guedes H M Amaro and F X Malcata ldquoMicroalgae assources of carotenoidsrdquoMarineDrugs vol 9 no 4 pp 625ndash6442011
[123] G L Renju G M Kurup and K C H Saritha ldquoEffect oflycopene from Chlorella marina on high cholesterol-inducedoxidative damage and inflammation in ratsrdquo Inflammopharma-cology vol 22 no 1 pp 45ndash54 2014
[124] G L Renju G M Kurup and C H S Kumari ldquoAnti-inflammatory activity of lycopene isolated from Chlorellamarina onType II Collagen induced arthritis in SpragueDawleyratsrdquo Immunopharmacology and Immunotoxicology vol 35 no2 pp 282ndash291 2013
[125] C Vılchez E Forjan M Cuaresma F Bedmar I Garbayo andJ M Vega ldquoMarine carotenoids biological functions andcommercial applicationsrdquo Marine Drugs vol 9 no 3 pp 319ndash333 2011
[126] G Richardson ldquoBeyond eye healthrdquo Life Extension Magazine2011 httpwwwleforgMagazine20117Beyond-Eye-HealthPage-01
[127] M Abidov Z Ramazanov R Seifulla and S Grachev ldquoTheeffects of Xanthigen in the weight management of obesepremenopausal women with non-alcoholic fatty liver diseaseand normal liver fatrdquo Diabetes Obesity and Metabolism vol 12no 1 pp 72ndash81 2010
[128] H M Ragap R H Khalil and H HMutawie ldquoImmunostimu-lant effects of dietary Spirulina platensis on tilapia Oreochromisniloticusrdquo Journal of Applied Pharmaceutical Science vol 2 no2 pp 26ndash31 2012
[129] W Xu Z Gao Z Qi M Qiu J-Q Peng and R Shao ldquoEffect ofdietary chlorella on the growth performance and physiologicalparameters of gibel carp Carassius auratus gibeliordquo TurkishJournal of Fisheries and Aquatic Sciences vol 14 no 1 pp 53ndash572014
[130] P Amaninejad H Emadi M Ematiazjoo et al ldquoEffects ofDunaliella microalgae (Dunaliella salina) on different level of
BioMed Research International 15
IgM Immunoglobulin in rainbow trout (Oncrohynchusmykiss)rdquoGlobal Journal of Biodiversity Science and Management vol 3no 2 pp 237ndash242 2013
[131] V Mimouni L Ulmann V Pasquet et al ldquoThe potential ofmicroalgae for the production of bioactive molecules of phar-maceutical interestrdquoCurrent Pharmaceutical Biotechnology vol13 no 15 pp 2733ndash2750 2012
[132] S M Tosh and S Yada ldquoDietary fibres in pulse seeds and frac-tions characterization functional attributes and applicationsrdquoFood Research International vol 43 no 2 pp 450ndash460 2010
[133] H M Amaro R Barros A C Guedes I Sousa-Pinto and FXMalcata ldquoMicroalgal compoundsmodulate carcinogenesis inthe gastrointestinal tractrdquo Trends in Biotechnology vol 31 no 2pp 92ndash98 2013
[134] S S M Mostafa ldquoMicroalgal biotechnology prospects andapplicationsrdquo in Plant Science chapter 12 pp 275ndash314 InTech2012
[135] L Custodio T Justo L Silvestre et al ldquoMicroalgae of dif-ferent phyla display antioxidant metal chelating and acetyl-cholinesterase inhibitory activitiesrdquoFoodChemistry vol 131 no1 pp 134ndash140 2012
[136] C-CHu J-T Lin F-J Lu F-P Chou andD-J Yang ldquoDetermi-nation of carotenoids in Dunaliella salina cultivated in Taiwanand antioxidant capacity of the algal carotenoid extractrdquo FoodChemistry vol 109 no 2 pp 439ndash446 2008
Figure 1 Spirulina sp LEB 18 from LEBFURG strains bank
21 Spirulina Spirulina (Arthrospira) is prokaryotic cyano-bacteria (Figure 1) that belongs to Cyanophyta which arosemore than 3 million years ago forming the current oxygenatmosphere and has been important in the regulation of theplanetary biosphere [21] In 1981 Spirulina was approved bythe FDA (Food Drug Administration) by the issuance of aGRAS (generally recognized as safe) certificate The FDA hasstated that Spirulina can be legally marketed as a food or foodsupplement without risk to human health [22]
Spirulina has a high protein value and high digestibilityand contains significant amounts of essential polyunsaturatedfatty acids and phenolic compounds [23] Due to proper-ties such as its high nutritional value and the presence ofactive biocompounds this microorganism is one of the moststudied microalgae worldwide [24] The Spirulina proteincontent ranges from 50 to 70 (ww) of its dry weight thecarbohydrate content from 10 to 20 (ww) and the lipidcontent from 5 to 10 (ww)
Thismicroalga is rich in vitamins B1 B2 B12 and E (espe-cially vitamin B12) Furthermore Spirulina has a high contentof pigments minerals and oligoelements (approximately 6to 9 (ww) biomass dry weight) of which the most impor-tant are iron calcium magnesium phosphorus and potas-sium [22] Some studies have demonstrated the use of thismicroalga for the production of pigments due to its antiox-idant properties [25ndash27] 120573-Carotene represents approxi-mately 80 of the carotenoids present in Spirulina andother components such as tocopherols phycocyanin andphycoerythrin are also part of its composition [13] Table 2shows some of the bioactive compounds that have beenextracted from Spirulina
Cyanobacteria are known to produce intracellular andextracellular metabolites with potential biological activitiessuch as antibacterial antifungal antiviral antitumor anti-HIV anti-inflammatory antioxidant antimalarial herbici-dal and immunosuppressant effects [13 28 29] The thera-peutic importance of Spirulina has been reported in severalstudies These include its use in the treatment of hyperlipi-demia cancer HIV diabetes obesity and hypertension theimprovement of immune response in renal protection againstheavy metals and drugs and the reduction in serum levels ofglucose and lipids among others [23 27 30 31]
Theworldrsquos largest producer Hainan Simai Pharmacy Co(China) annually produces 3000 tonnes of Spirulina biomass
Figure 2 Microalga Nostoc ellipsosporum from LEBFURG strainsbank
[13] One of the largest industries in the world is EarthriseFarms (California USA) (httpwwwearthrisecom) Manyother companies market a wide variety of nutraceuticalproducts produced from these microalgae For example theMyanmar Spirulina Factory (Yangon Myanmar) producespills French fries and pasta Cyanotech (Hawaii USA)produces and markets products under the name SpirulinaPacifica (httpwwwcyanotechcom) In Brazil the OlsonMicroalgas Macronutricao company (Camaqua Rio Grandedo Sul) produces Spirulina sp LEB 18 capsules for sale as adietary supplement (httpwwwolsoncombr)
22 Nostoc Nostoc is an edible microalga that belongs to theNostocaceae group Cyanophyta that forms spherical coloniesthat link together as filamentsThismicroalga has heterocystswith a pattern of homogeneous cells and a regular distancebetween cells that compose the filament (Figure 2) [32] Theheterocysts fix atmospheric nitrogen for amino acid synthesisin themicroalgal biomass In the absence of a nitrogen sourceduring microalgal cultivation heterocysts form avoiding thelimitation of this nutrient for cell growth [33]
Nostoc microalgal biomass has been used in the medicalfield and as a dietary supplement because of its proteinvitamin and fatty acid content The medical value of thismicroalga was evidenced by its use in the treatment of fistulaand for some forms of cancer [34]Historically the biomass ofthis microorganism is described as anti-inflammatory and italso aids in digestion blood pressure control and immuneboosting Several studies suggest thatNostoc produces severalcompounds with antimicrobial antiviral and anticanceractivity These results have encouraged its cultivation on alarge scale and it has great economic potential due to itsnutritional and pharmaceutical importance [35] Table 3presents some bioactive compounds that have been extractedfrom the microalga of the Nostoc genus
Cyanovirin a potential protein molecule produced by aNostocmicroalga showed a positive effect in the treatment ofHIV [36] and Influenza A (H1N1) [6] Nostoc contains aspectrum of polyunsaturated fatty acids (PUFAs) that includeessential fatty acids such as linoleic 120572-linolenic 120574-linolenicoctadecatetraenoic and eicosapentaenoic acid [37] Essentialfatty acids are precursors of prostaglandins engenderingsignificant interest from the pharmaceutical industry
4 BioMed Research International
Table 2 Bioactive compounds extracted from Spirulina genus
23 Chlorella Spirulina and Chlorella represent the majorityof themicroalgal biomass market with an annual productionof 3000 and 4000 tons respectively [38] Chlorella sp isa eukaryotic genus of green unicellular microalgae thatbelongs to the Chlorophyta group (Figure 3) [39]
This microalga was discovered by the Japanese tradi-tional consumers of algae who usually enjoy it and use itas a food supplement The microalga Chlorella is rich inchlorophyll proteins polysaccharides vitamins mineralsand essential amino acids This microalga is 53 (ww)protein 23 (ww) carbohydrate 9 (ww) lipids and 5(ww) minerals and oligoelements [22]
These nutrient concentrations can be varied by manipu-lation of culture conditions The biomass of this microalga isalso rich in B complex vitamins especially B12 which arevital in the formation and regeneration of blood cells LikeSpirulina Chlorella has a GRAS certificate issued by the FDAand can thus be used as a food without risk to human healthwhen grown in a suitable environment with proper hygieneand good manufacturing practices [22 40]
Chlorella contains bioactive substances with medicinalproperties Experimental studies with Chlorella demon-strated their antitumor anticoagulant antibacterial antiox-idant and antihiperlipidemia effects in addition to a hepato-protective property and the immunostimulatory activity ofenzymatic protein hydrolyzate [39 41ndash44]
Many antioxidant compounds may be responsible forChlorella functional activities Antioxidants such as lutein 120572-carotene 120573-carotene ascorbic acid and 120572-tocopherol whichare active against free radicals were identified Some of thesecompounds not only are important as natural colorants oradditives but also may be useful in reducing the incidence ofcancer and in the prevention ofmacular degeneration [39 45](Table 4)
The most important bioactive compound in Chlorellais 120573-13 glucan an active immunostimulator that reducesfree radicals and blood cholesterol The efficacy of thiscompound against gastric ulcers sores and constipation hasbeen reported It also has been demonstrated to have preven-tive action against atherosclerosis and hypercholesterolemia
BioMed Research International 5
Table 4 Bioactive compounds extracted from the microalgae of the Chlorella genus
as well as antitumor activity [46] Chlorella is produced bymore than 70 companies Taiwan Chlorella ManufacturingCo (Taipei Taiwan) is the worldrsquos largest producer ofChlorella with over 400000 tons of biomass producedper year (httpwwwtaiwanchlorellacomindexphp) Sig-nificant production also occurs in Klotze (Germany) (80ndash100 t yrminus1 of dry biomass) [47]
24 Dunaliella Dunaliella is a green unicellular halotol-erant microalga that belongs to the Chlorophyceae group(Figure 4) This microalga is widely studied due to its tol-erance of extreme habitat conditions physiological aspectsand its many biotechnological applications Dunaliella is asource of carotenoids glycerol lipids and other bioactivecompounds such as enzymes and vitamins [48 49]
This microalga is a major source of natural 120573-caroteneable to produce up to 14 of its dry weight under conditionsof high salinity light and temperature as well as nutrientlimitation [50] In addition to 120573-carotene this microalgais rich in protein and essential fatty acids which can beconsumed safely as evidenced by GRAS recognition [22]Table 5 presents some compounds that have been extractedfrom microalgae of the Dunaliella genus
Compounds in the Dunaliella biomass have various bio-logical activities such as antioxidant antihypertensive bron-chodilatory analgesic muscle relaxant hepatoprotective andantiedemal properties The microalgal biomass can also be
used directly in food and pharmaceutical formulations [2251]
Chang et al [52] showed that Dunaliella cells containedantibiotic substances According to these authors the crudeextract of this microalga strongly inhibited the growthof Staphylococcus aureus Bacillus cereus Bacillus subtilisand Enterobacter aerogenes In another study Dunaliellamicroalga also showed antibacterial activity against variousmicroorganisms of importance to the food industry includ-ing Escherichia coli Staphylococcus aureus Candida albicansand Aspergillus niger [49 53]
Under ideal growing conditions Dunaliella can be stim-ulated to produce approximately 400mg of 120573-carotene persquare meter of growing area The cultivation of Dunaliellafor the production of 120573-carotene has been conducted inseveral countries including Australia Israel the USA andChina [54ndash56] An ingredient of Dunaliella with a strongability to stimulate cell proliferation and improve the energymetabolism of the skin was released by Pentapharm (BaselSwitzerland) [57] New pilot plants are under development inIndia Chile Mexico Cuba Iran Taiwan Japan Spain andKuwait [50]
3 Cultivation Conditions
The conditions for microalgal cultivation are important fac-tors that influence the metabolism of these microorganismsthus directing the synthesis of specific compounds of interestSeveral researchers have noted the influence of incubationtemperature the pH of themedium the period of cultivationaswell as salinity light intensity andmediumconstituents onthe synthesis of antimicrobial agents [58]
31 pH Temperature and Luminescence pH adjustments arethe primary measures used to prevent contamination bymicroorganisms such as other microalgae species pH con-trol is also essential for effective absorption of the compo-nents of the culture medium because it directly affects theavailability of various chemical elements [59] The reductionof some nutrients in the culturemedium can lead the produc-ing of specific biocompounds The difficulty of consuminga nitrogen source for example can lead microalgae to shiftyourmetabolism for lipids or carbohydrates production [60]
Light is an indispensable factor for photosynthesis caus-ing the cells to reproduce and thereby increasing the cell
6 BioMed Research International
Table 5 Bioactive compounds extracted from the microalgae of the Dunaliella genus
concentration [61] The illuminance also influences the bio-chemical composition of the biomass [62] The fatty acidcontent can be reducedwith increasing light incidenceThis isbecause lipids are the major components of chloroplasts andthe increased light energy demand greater activity of chloro-plasts [63] Studies also show the influence of illuminanceon the microalgae antioxidants According to Madhyastha[64] the application of blue light in the cultivation of themicroalga Spirulina fusiformis through a phenomenon wherethe microalgae cells alter the sequence of amino acids withcysteine repeats enhanced the antioxidant capacity
One of the most important factors for the growth of allliving organisms is the temperature The specific growth rateof the microalgae is directly correlated with the gross rate ofCO2
fixationO2
production (photosynthesis) and the respi-ration rate Photosynthesis and respiration are temperature-dependent with the respiration rate increasing exponentiallywith temperature [65] Temperature has a great influenceon the production of biomass proteins lipids and phenoliccompounds from microalgae The optimum temperature forcultivation of microalgae is 35ndash37∘C [66] In studies con-ducted by Noaman [58] that were performed to verifywhich culture conditions stimulated the greatest produc-tion of antimicrobial agents by the microalga Synechococcusleopoliensis it was observed that a temperature of 35∘C andpH 8 produced a maximum concentration of this bioactivecompound
32 Bioreactors Microalgae have attracted much interest forproduction of bioactive compounds and in order to growand tap the potentials of algae efficient photobioreactors arerequired A good number of photobioreactors can be used inproduction of various algal products [67] Innovative culti-vation systems andmodification of biochemical compositionof microalgae by simple changes in the growth media andcultivation conditions (nutrients light intensity temperaturepH mixing etc) can lead to higher productivity of thetargeted products [68]
Bioreactors can be classified as open or closed Closedphotobioreactors have attracted much interest because theyallow a better control of the cultivation conditions than opensystems One of the major advantages of open ponds is thatthey are easier to construct and operate than most closedsystems [67]
In open systems temperature is a main limiting factoras are variations in solar radiation that lead to low biomassconcentrations However open systems are the most widely
used due to their economic viability Closed systems aregenerally used on a pilot scale for investigating problemsrelated to economic viability Furthermore the use of closedsystems is primarily used for microalgal species that do notgrow in a highly selective medium avoiding contaminationof the cultures [69]
Closed bioreactors can provide high productivity gen-erating greater microalgal biomass per unit time Otheradvantages of the use of closed bioreactors compared withopen systems include the following (i) virtually zero losses inconnection with evaporation (ii) a marked reduction ofproblems related to culture contamination by heterotrophicalgae or othermicroorganisms (iii) ease of biomass collectionprocedures due to smaller volumes of culture medium (iv)greater control of gas exchange between the culture andthe atmosphere (v) a smaller occupied space (vi) a highsurfacevolume ratio which helps to increase the illuminationof the system and (vii) the possibility of obtaining high puritycultures [59]
33 Nutrients The metabolism of microalgae can beautotrophic or heterotrophic The former requires onlyinorganic compounds such as CO
2
salts and solar energythe latter is not photosynthetic requiring an external sourceof organic compounds for use as a nutrient and energy sourceSome photosynthetic species are mixotrophic having theability to perform photosynthesis and use exogenous organicsources simultaneously [70]
Microalgae react to changes in their external environmentwith changes in their intracellular environment Thus themanipulation of the culture conditions or the presence orabsence of nutrients stimulates the biosynthesis of specificcompounds This fact was first referenced by Richmond[71] who changed the composition of Chlorella biomassparticularly in their protein and lipid content by varyingcultivation conditions
Noaman [58] found that leucine combined with citrateor acetate is the sources of nitrogen and carbon that pro-duced higher concentrations of antimicrobial agents in themicroalga Synechococcus leopoliensis Coca et al [72] study-ing the cultivation of Spirulina platensis in a medium sup-plemented with vinasse obtained an increased protein yieldcompared to the unsupplemented culture medium Ip andChen [73] studying the cultivation of Chlorella zofingiensisunder mixotrophic cultivation conditions found that lowconcentrations of nitrate and a high glucose concentrationfavored the production of astaxanthin in this microalga
BioMed Research International 7
Alonso et al [74] studying the influence of nitrogen con-centration in continuous cultivation on lipid concentrationin Phaeodactylum tricornutum noted that there was accu-mulation of saturated and unsaturated fatty acids when thenitrogen source was reduced
Culture media are chemical preparations that are formu-lated to contain the nutrients necessary for the microorgan-isms to multiply andor survive The culture media shouldmeet the nutritional needs of the microorganism assist inprocess control and have a reasonably fixed composition[75]
Among different microalgae variations in the culturemedium are mainly related to the amount of necessary nutri-ents Even so nutritional needs are dependent on environ-mental conditions [59] Microalgae require macronutrientssuch as C N O H P Ca Mg S and K for their growthThe micronutrients that are generally required are Fe MnCu Mo and Co Additionally some species require lowerconcentrations of vitamins in the culture medium [76]
4 Advantages of Using Microalgae to ObtainBioactive Compounds
Microalgae are important sources of bioactive natural sub-stances Many metabolites isolated from these microorgan-isms have shown biological activities and potential healthbenefits [77] Microalgae accumulate specific secondarymetabolites (such as pigments and vitamins) which are highvalue products that have applications in the cosmetic foodor pharmaceutical industries [8 78]
Microalgae live in complex habitats and are subjectedto stress andor extreme conditions such as changes insalinity temperature and nutrients Thus these microorgan-isms must rapidly adapt to new environmental conditions tosurvive and thus produce a great variety of biologically activesecondary metabolites that are not found in other organisms[79] Some of the advantages of microalgal cultivation maybe associated with taxonomic diversity the diverse chemicalcomposition the potential for growth in a bioreactor undercontrolled conditions and the ability to produce activesecondary metabolites in response to the stress induced byextreme exposure conditions [39 80]
In addition to their natural characteristics other impor-tant aspects related to microalgae are the use of solar energyand carbon dioxide (CO
2
) and a high growth rate whichcan produce higher yields compared to higher plants Inaddition microalgae can be grown in areas and climates thatare unsuitable for agriculture therefore microalgae do notcompete with arable food production land The possibility ofcontrolling the production of certain bioactive compoundsby manipulation of culture conditions is another advantageof using microalgae [7 81ndash83]
The cultivation of microalgae is a major mechanism forreducing excess carbon dioxide (CO
2
) in the atmosphere bybiofixation in which an industrial process uses a CO
2
-richgas as a carbon source formicroalgal growthThismechanismcontributes to a reduction of the greenhouse effect and globalwarming further reducing the costs of the carbon source
for growth which is the greatest nutrient requirement formicroalgae [13 84]
The cultivation of microalgae is not seasonal they areimportant for food in aquaculture systems and can effectivelyremove pollutants such as nitrogen and phosphorus fromwastewater Moreover they are themost efficient solar energybiomass converters Microalgae cultivation via sunlight-dependent systems contributes to sustainable developmentand natural resource management [13]
The integration of the production process of bioactivemetabolites in a biorefinery is a sustainable means of energyproduction food production and the production of productswith high added value [7] The biorefinery concept based onmicroalgae depends on the efficient use of biomass throughfractionation resulting in several isolated productsThis con-cept encompasses a biorefinery platform which is capable ofoffering a wide variety of different products such as productswith applications in pharmaceuticals medicine food (pro-tein fiber) and biofuels [7 85] These benefits contribute tothe economic viability of microalgal production [7 8]
5 Bioactive Compounds
Bioactive compounds are physiologically active substanceswith functional properties in the human body There is greatenthusiasm for the development and manufacture of variousbiocompounds that can potentially be used as functionalingredients such as carotenoids phycocyanins polyphenolsfatty acids and polyunsaturated compounds [16]
An interest in the production of bioactive compoundsfrom natural sources has recently emerged driven by agrowing number of scientific studies that demonstrate thebeneficial effects of these compounds on health [80] Naturalproducts are important in the search for new pharmaco-logically active compounds In general they play a role indrug discovery for the treatment of human diseases [86]Many clinically viable and commercially available drugs withantitumor and antiinfective activity originated as naturalproducts
Microalgae are a natural source of interesting biocom-pounds Microalgae are known to produce various therapeu-tically effective biocompounds that can be obtained from thebiomass or released extracellularly into the medium [11]These microorganisms contain many bioactive compoundssuch as proteins polysaccharides lipids vitamins enzymessterols and other high-value compounds with pharmaceu-tical and nutritional importance that can be employed forcommercial use [13]
51 Compounds with Antioxidant Function Oxidative dam-age caused by reactive oxygen species to lipids proteins andnucleic acids can cause many chronic diseases such as heartdisease atherosclerosis cancer and aging Epidemiologicalstudies have demonstrated an inverse association between theintake of fruits and vegetables and mortality from diseasessuch as cancer This phenomenon can be attributed to theantioxidant activity of these foods [87]
8 BioMed Research International
Microalgal biomass is considered a rich natural source ofantioxidants with potential applications in food cosmet-ics and medicine [87] Antioxidant compounds such asdimethylsulfoniopropionate and mycosporine amino acidswere isolated frommicroalgae and are potent chemical block-ers ofUV radiation [88] In addition to these compounds pig-ments lipids and polysaccharides with antioxidant activitycan also be found in microalgal biomass
Carotenoids and phycocyanins are the pigments mostused in scientific research C-phycocyanin (C-PC) is a bluephotosynthetic pigment that belongs to the group of phyco-biliproteins found in large quantities in the cyanobacteriaRhodophyta and Cryptophyte [89] Phycocyanin has appli-cations as a nutrient and natural food colorants and cosmet-ics It is usually extracted from the biomass of Spirulina [90]and Porphyridium cruentum [91] and Synechococcus [89]
Among the carotenoid compounds 120573-carotene andastaxanthin are prominent These compounds have appli-cation in the food and pharmaceutical industries becauseof their antioxidant properties and pigmentation ability Inmicroalgal metabolism they protect photosynthetic tissuesagainst damage caused by light and oxygen [92] Dunaliellasalina is a microalga recognized as a major biological sourceof 120573-carotene pigment producing more than 14 in drybiomass [46] H pluvialis is a source of the pigment astax-anthin producing 1ndash8 of astaxanthin as dry biomass [93]
Polysaccharides represent a class of high value-addedcomponents with applications in food cosmetics fabrics sta-bilizers emulsifiers and medicine [94] Microalgal polysac-charides contain sulphate esters are referred to as sulfatedpolysaccharides and possess unique medical applicationsThe basic mechanism of therapeutic action is based on thestimulation of macrophages and modulation The biologicalactivity of sulfur polysaccharides is linked to their sugarcomposition position and degree of sulfation [95] Amongthe microalgae capable of producing these compounds areChlorella vulgaris Scenedesmus quadricauda [96] and Por-phyridium sp [97]
52 Compounds with Antimicrobial Activity The importanceof discovering new compounds with antimicrobial activityis driven by the development of antibiotic resistance inhumans due to constant clinical use of antibioticsMicroalgaeare an important source of antibiotics with a broad andefficient antibacterial activity [11] The antimicrobial activityof these microorganisms is due to the ability to synthesizecompounds such as fatty acids acrylic acids halogenatedaliphatic compounds terpenoids sterols sulfur-containingheterocyclic compounds carbohydrates acetogenins andphenols [98]
The antimicrobial activity of extracts from microalgae isrelated to its lipid composition The antimicrobial action ofmicroalgae is also noteworthy because of the potential toproduce compounds such as 120572- and 120573-ionone 120573-cyclocitralneophytadiene and phytol [99] Microalgae antimicrobialactivity against human pathogens such as Escherichia coliPseudomonas aeruginosa Staphylococcus aureus and Staphy-lococcus epidermidis has been attributed to 120574-linolenic acid
The mechanism of action of fatty acids affects variousstructures in microorganisms however cell membranes arethe most impacted Membrane damage most likely leadsto a loss of internal substances from the cells and theentry of harmful components reduces nutrient absorption inaddition to inhibiting cellular respiration The ability of fattyacids to interfere with bacterial growth depends on boththeir chain length and the degree of unsaturation Fatty acidswith more than 10 carbon atoms apparently induce lysis ofbacterial protoplasts [99]
Microbial polysaccharides and other biological com-pounds have antiviral and antimicrobial action Microalgaeproduce extracellular sulfated polysaccharide (EPS) withacidic characteristics that has a potential as a therapeuticagent [101] Highly sulfated antiviral polysaccharides fromseveral species of microalgae consist mainly of xylose glu-cose and galactose The EPS sulfate groups determine somecharacteristics of polysaccharides it has been found thathigher sulphate contents induced higher antiviral activities[94 101] The inhibitory effect of polysaccharides of microal-gal origin is due to viral interactions or positive charges onthe cell surface thereby preventing penetration of the virusinto host cells [99]
The cyanobacterium Spirulina (Arthrospira) can producesulfated polysaccharides that have already found applicationsas antiviral agents both in vivo and in vitro [102] Eukaryoticmicroalgae such as Chlorella sp and Dunaliella sp produceand secrete polysaccharides at relatively high levels [17] Theantibacterial ability of Spirulina has been correlated withtheir volatile composition resulting in the identification of15 elements which constitutes 96 of total compounds Themajor volatile components produced by Spirulina consist ofheptadecane (40) and tetradecane (35) [39]
Some studies have reported that sulfated polysaccharidesderived from microalgae inhibit viral infection such asencephalomyocarditis virus Herpes simplex virus types 1and 2 (HSV1 HSV2) human immunodeficiency virus (HIV)hemorrhagic septicemia in salmonid virus swine fever virusand varicella virus [99 103] Carrageenan is a sulfatedpolysaccharide that can directly bind to human papillo-mavirus to inhibit not only the viral adsorption process butalso the input and subsequent process of the uncoating of thevirus [101]
53 Compounds with Anti-Inflammatory Action Inflam-mation is an immediate reaction to a cell or tissueinjury caused by noxious stimuli such as toxins andpathogens In this situation the body recognizes theagents responsible for the attack and attempts to neu-tralize them as quickly as possible Inflammation causesredness swelling heat and pain usually located at thesite of infection [104] Ingestion of anti-inflammatory com-pounds enhances the bodyrsquos immune response and helpsto prevent disease and aids the healing process Microal-gae produce several anti-inflammatory compounds in their
BioMed Research International 9
biomass that may exert a protective function in the bodywhen consumed as food or used as pharmaceuticals andcosmetics
Because of its anti-inflammatory capabilities microalgalbiomass is being considered for applications in tissue engi-neering for the development of scaffolds for use in reconsti-tution of organs and tissues [105 106] This is an importantapplication for humans especially in patients with burnsin which the skin was completely lost [107] Among themost important microalgal compounds with such prop-erties are long-chain polyunsaturated fatty acids (PUFAs)[108 109] sulfurized polysaccharides [110] and pigments[111]
Many microalgal polysaccharides possess the ability tomodulate the immune system through the activation ofmacrophage functions and the induction of reactive oxy-gen species (ROS) nitric oxide (NO) and various othertypes of cytokineschemokines [112] Macrophages are ableto regulate several innate responses and secrete cytokinesand chemocytokines that serve as signals for immune andinflammatory molecular reactions [113] Sulfur polysaccha-rides with anti-inflammatory activity can be applied inskin treatments inhibiting the migration and adhesion ofpolymorphonuclear leukocytes [110] Guzman et al [114]studied the anti-inflammatory capacity of the microalgaChlorella stigmatophora and Phaeodactylum tricomutum andconcluded that bothmicroalgae showed positive responses inthe test of paw edema by carrageenan
The PUFAs especially 1205963 and 1205966 as eicosapentaenoic(EPA) docosahexaenoic (DHA) and arachidonic (AA) acidshave been applied in the treatment of chronic inflammationsuch as rheumatism and skin diseases [108] Ryckebosch etal [115] evaluated the nutritional value of the total lipidsextracted from different PUFAs produced by microalgae Inthis study the microalgae IsochrysisNannochloropsis Phaeo-dactylum Pavlova and Thalassiosira produced 1205963 PUFA asan alternative to fish oil in food
Among the pigments with anti-inflammatory activityfucoxanthin carotenoid found in diatoms [116 117] is capableof stimulating apoptosis in human cancer cells [118] A phy-cocyanin found in cyanobacteria has an anti-inflammatoryactivity that occurs through the inhibition of histaminerelease [111 119]
54 Compounds with Potentiality over Degenerative Dis-eases In humans the oxidation reactions driven by reactiveoxygen species (ROS) can lead to irreversible damage tocellular components including lipids proteins and DNAdegradation andor mutation Consequently this damagecan lead to several syndromes such as cardiovascular dis-ease some cancers and the degenerative diseases of aging[120]
Chronic age-related diseases involve oxidative stress andinflammation and their consequences Chronic inflammationplays a significant role in the mediation of neurodegenerativediseases such as Parkinsonrsquos disease Alzheimerrsquos diseasemultiple sclerosis acquired immunodeficiency syndrome(AIDS) and dementia complex [77]
Natural pigments derived from microalgae (NPs) haveneuroprotective properties being valuable sources as func-tional ingredients in foods and pharmaceutical products thatshow efficient action in the treatment andor prevention ofneurodegenerative diseases Vitamin E has preventive effectsfor many diseases such as atherosclerosis and heart diseaseas well as neurodegenerative diseases such as multiplesclerosis [77]
Carotenoids have great potential benefits to humanhealth including the treatment of degenerative diseases suchas macular degeneration and cataract development Thesecompounds act as antioxidants reducing oxidative damageby ROS Studies indicated that increased intake of phenolsdecreased the occurrence of degenerative diseases Phenoliccompounds from microalgae with the potential to fight freeradicals have been reported [121]
Dunaliella salina is a natural source of 120573-carotene whichproduced a reduced risk of cancer and degenerative diseasesin humans Lutein is effective against various diseases includ-ing cataracts and macular degeneration and in the earlystages of atherosclerosis Extracts of Chlorella sp containing120573-carotene and lutein significantly prevented the cognitivedisability that accompanies Alzheimerrsquos disease in rats It wasalso reported that lutein extracted from Chlorella reducedthe incidence of cancer Likewise carotenoids extractedfrom Chlorella ellipsoidea and Chlorella vulgaris inhibited thegrowth of colon cancer [122] A lycopene extracted fromthe microalgae Chlorella marina significantly reduced theproliferation of prostate cancer inmice [123]This compoundalso reduced total cholesterol and low-density lipoprotein(LDL) levels [123] and improved rheumatoid arthritis [124]
Low plasma levels of lutein have also been associatedwith an increased tendency ofmyocardial infarction whereashigh intake of lutein was related to a decreased risk ofstroke In addition high levels of carotenoids with provi-tamin A activity including 120572-carotene 120573-carotene and 120573-cryptoxanthin have been associated with reduction in therisk of angina pectoris Macular degeneration the lead-ing cause of irreversible vision loss has also been associ-ated with very low consumption of lutein and zeaxanthin[125]
Scientific findings indicate astaxanthin for multimodalintervention formany forms of degenerative diseases includ-ing cardiovascular diseases cancer metabolic syndromecognitive impairment age-related immune dysfunctionstomach and ocular diseases (macular degeneration cataractglaucoma diabetic retinopathy and retinitis pigmentosa)and skin damage [126] High levels of lycopene in plasmaand tissues were inversely related to coronary heart diseasemyocardial infarction and the risk of atherosclerosis [125]
55 Compounds withHealth Promoting Function The impor-tance of microalgae as sources of functional ingredients hasbeen recognized because of their beneficial health effectsNatural pigments are valuable sources of bioactive com-pounds These pigments have various beneficial biologicalactivities such as antioxidant anticancer anti-inflammatoryantiobesity antiangiogenic and neuroprotective action and
10 BioMed Research International
are indicated for the treatment or prevention of severalchronic diseases [77]
The antioxidant potential of carotenoid pigments andtheir ability to prevent cancer aging atherosclerosis coro-nary heart disease and degenerative diseases have beendescribed 120573-Carotene has higher provitamin A activitywhich is essential for vision and the correct functioning ofthe immune system Astaxanthin is linked to many healthbenefits such as protection against lipid peroxidation age-related macular degeneration reduced atherosclerosis andan increased immune response [102]
Fucoxanthin is considered as a promising dietary andweight loss supplement and for the treatment of obesityClinical studies by Abidov et al [127] demonstrated the effectof ldquoxanthigenrdquo a fucoxanthin based antiobesity supplementFurthermore fucoxanthinmay be useful for the prevention ofbone diseases such as osteoporosis and rheumatoid arthritisIt has also been reported to be effective for the therapeutictreatment of diabetic diseases suppressing insulin and hyper-glycemia [77]
Microalgae proteins are of great interest as a source ofbioactive peptides due to their therapeutic potential in thetreatment of various diseases [7] Proteins peptides andamino acids have functions that contribute to health benefitsThese compounds can include growth factors hormones andimmunomodulators and can help to replace damaged tissuesin addition to providing nutritional benefits Microalgaesuch as Chlorella and Spirulina (Arthrospira) may be usedas nutraceuticals or included in functional foods to preventdiseases and damage to cells and tissues due to their richprotein content and amino acid profile [102]
The antimicrobial action of certain enzymes (eglysozyme) and immunoglobulins has been reported andrecommended for people with different diseases (egCrohnrsquos disease) due to the existence of formulations withpeptides and free amino acids Studies of the healtheffects of lysozyme have been reported in the microalgaeSpirulina platensis [128] Chlorella [129] and Dunaliellasalina [130] Spirulina (Arthrospira) and Chlorella biomasspills are marketed as is ldquoHawaiian Spirulina Pacificardquo(httpspirulinagreennutritionalscomau) Other proteinscan also increase the production of cholecystokinin involvedin appetite suppression and the reduction of LDL-cholesterolProtein peptides from Chlorella have a potential as dietarysupplements for the prevention of oxidative stress-relateddiseases such as atherosclerosis coronary heart disease andcancer [39]
The essential fatty acids 120596-3 and 120596-6 in particular areimportant for the integrity of tissues 120574-Linolenic acid hastherapeutic applications in cosmetics to revitalize the skinand thus slow aging Linoleic and linolenic acids are essentialnutrients for the immune system and other related tissueregeneration processes Linoleic acid is also used for thetreatment of hyperplasia of the skin [102]
The most studied microalgal lipid compounds are thepolyunsaturated fatty acids (PUFAs) docosahexaenoic acid(120596-3 C226) (DHA) eicosapentaenoic acid (C20 120596-35)(EPA) and arachidonic acid (120596-6 C204) (ARA) Studies haveshown that dietary120596-3 PUFAs have a protective effect against
atherosclerotic heart disease [131] DHA and EPA showed theability to reduce problems associated with strokes and arthri-tis besides reducing hypertension lipid content (a decreasein triglycerides and an increase of HDL) and acting asanti-inflammatory agents DHA is also important in thedevelopment and function of the nervous system Further-more ARA and EPA are platelet aggregators vasoconstric-tors and vasodilators and have antiaggregative action on theendothelium as well as chemostatic activity in neutrophils[102]
Other lipid compounds with interesting bioactive prop-erties are the microalgal sterols Phytosterols have demon-strated reduction of total cholesterol (LDL) in humans byinhibiting its absorption from the intestine [50] Polysac-charides can be considered as dietary fibers associatedwith different physiological effects Insoluble fiber (cellulosehemicellulose and lignin) mainly promotes the movementof material through the digestive system thereby improvinglaxation and increasing satietyThey can also be considered asprebiotics because they promote the growth of gutmicrofloraincluding probiotic species Soluble fiber (oligosaccharidespectins and 120573-glucans) may reduce cholesterol and regulateblood glucose [7 132]
6 Conclusion
The proven ability of microalgae to produce bioactive com-pounds places these microorganisms in the biotechnologicalspotlight for applications in various areas of study especiallyin the life sciencesThe production ofmicroalgal metaboliteswhich stimulate defense mechanisms in the human bodyhas spurred intense study of the application of microalgalbiomass in various foods and pharmacological and medicalproducts There is obviously a need for further study of theidentified compounds and their activities in the treatmentand prevention of various diseases in addition to an ongoingsearch for other as yet undetected metabolites
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgment
The authors thank the National Counsel of Technologicaland Scientific Development (CNPq) for the Productivityin Technological Development and Innovative ExtensionScholarship
References
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[2] A A El Gamal ldquoBiological importance of marine algaerdquo SaudiPharmaceutical Journal vol 18 no 1 pp 1ndash25 2010
BioMed Research International 11
[3] I Moreno-Garrido ldquoMicroalgae immobilization current tech-niques and usesrdquo Bioresource Technology vol 99 no 10 pp3949ndash3964 2008
[4] R-B Volk and F H Furkert ldquoAntialgal antibacterial andantifungal activity of two metabolites produced and excretedby cyanobacteria during growthrdquoMicrobiological Research vol161 no 2 pp 180ndash186 2006
[5] R-B Volk ldquoA newly developed assay for the quantitativedetermination of antimicrobial (anticyanobacterial) activity ofboth hydrophilic and lipophilic test compounds without anyrestrictionrdquoMicrobiological Research vol 163 no 2 pp 161ndash1672008
[6] D F Smee K W Bailey M-H Wong et al ldquoTreatment ofinfluenza A (H1N1) virus infections in mice and ferrets withcyanovirin-Nrdquo Antiviral Research vol 80 no 3 pp 266ndash2712008
[7] E Ibanez and A Cifuentes ldquoBenefits of using algae as naturalsources of functional ingredientsrdquo Journal of the Science of Foodand Agriculture vol 93 no 4 pp 703ndash709 2013
[8] G Markou and E Nerantzis ldquoMicroalgae for high-valuecompounds and biofuels production a review with focus oncultivation under stress conditionsrdquo Biotechnology Advancesvol 31 no 8 pp 1532ndash1542 2013
[9] R Harun M Singh G M Forde andM K Danquah ldquoBiopro-cess engineering ofmicroalgae to produce a variety of consumerproductsrdquo Renewable and Sustainable Energy Reviews vol 14no 3 pp 1037ndash1047 2010
[10] C Kolympiris N Kalaitzandonakes and D Miller ldquoPublicfunds and local biotechnology firm creationrdquo Research Policyvol 43 no 1 pp 121ndash137 2014
[11] S Bhagavathy P Sumathi and I Jancy Sherene Bell ldquoGreenalgae Chlorococcum humicola-a new source of bioactive com-pounds with antimicrobial activityrdquo Asian Pacific Journal ofTropical Biomedicine vol 1 no 1 pp S1ndashS7 2011
[12] A M F Palavra J P Coelho J G Barroso et al ldquoSupercrit-ical carbon dioxide extraction of bioactive compounds frommicroalgae and volatile oils from aromatic plantsrdquo Journal ofSupercritical Fluids vol 60 pp 21ndash27 2011
[13] I Priyadarshani and B Rath ldquoCommercial and industrialapplications of micro algaemdasha reviewrdquo Journal of Algal BiomassUtilization vol 3 no 4 pp 89ndash100 2012
[14] JW Blunt B R CoppM H GMunro P T Northcote andMR Prinsep ldquoMarine natural productsrdquoNatural Product Reportsvol 23 no 1 pp 26ndash78 2006
[15] A M S Mayer and M T Hamann ldquoMarine pharmacologyin 2001-2002 marine compounds with anthelmintic antibacte-rial anticoagulant antidiabetic antifungal anti-inflammatoryantimalarial antiplatelet antiprotozoal antituberculosis andantiviral activities affecting the cardiovascular immune andnervous systems and other miscellaneous mechanisms ofactionrdquo Comparative Biochemistry and Physiology Part C Toxi-cology amp Pharmacology vol 140 no 3-4 pp 265ndash286 2005
[16] M Plaza S Santoyo L Jaime et al ldquoScreening for bioactivecompounds from algaerdquo Journal of Pharmaceutical and Biomed-ical Analysis vol 51 no 2 pp 450ndash455 2010
[17] I Rodrıguez-Meizoso L Jaime S Santoyo et al ldquoPressurizedfluid extraction of bioactive compounds from Phormidiumspeciesrdquo Journal of Agricultural and Food Chemistry vol 56 no10 pp 3517ndash3523 2008
[18] L R Carvalho A Costa-Neves G A A Conserva et alldquoBiologically active compounds from cyano bacteria extracts in
vivo and in vitro aspectsrdquo Brazilian Journal of Pharmacognosyvol 23 no 3 pp 471ndash480 2013
[19] B Nobre FMarcelo R Passos et al ldquoSupercritical carbon diox-ide extraction of astaxanthin and other carotenoids from themicroalga Haematococcus pluvialisrdquo European Food Researchand Technology vol 223 no 6 pp 787ndash790 2006
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extraction of 120574-linolenic acid and other lipids from Arthrospira(Spirulina)maxima comparison with organic solvent extrac-tionrdquo Food Chemistry vol 99 no 1 pp 57ndash63 2006
[21] I Romano M R Bellitti B Nicolaus et al ldquoLipid profilea useful chemotaxonomic marker for classification of a newcyanobacterium in Spirulina genusrdquo Phytochemistry vol 54 no3 pp 289ndash294 2000
[22] J A C Costa and M G Morais ldquoMicroalgae for food produc-tionrdquo in Fermentation Process Engineering in the Food IndustryC R Soccol A Pandey and C Larroche Eds p 486 Taylor ampFrancis 2013
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[25] F S Antelo J A V Costa and S J Kalil ldquoThermal degradationkinetics of the phycocyanin from Spirulina platensisrdquo Biochem-ical Engineering Journal vol 41 no 1 pp 43ndash47 2008
[26] S T Silveira J F M Burkert J A V Costa C A V Burkertand S J Kalil ldquoOptimization of phycocyanin extraction fromSpirulina platensis using factorial designrdquo Bioresource Technol-ogy vol 98 no 8 pp 1629ndash1634 2007
[27] L M Colla C O Reinehr C Reichert and J A V Costa ldquoPro-duction of biomass and nutraceutical compounds by Spirulinaplatensis under different temperature and nitrogen regimesrdquoBioresource Technology vol 98 no 7 pp 1489ndash1493 2007
[28] R P Rastogi and R P Sinha ldquoBiotechnological and industrialsignificance of cyanobacterial secondary metabolitesrdquo Biotech-nology Advances vol 27 no 4 pp 521ndash539 2009
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[30] L M Colla A L Muccillo-Baisch and J A Vieira CostaldquoSpirulina platensis effects on the levels of total cholesterol HDLand triacylglycerols in rabbits fed with a hypercholesterolemicdietrdquo Brazilian Archives of Biology and Technology vol 51 no 2pp 405ndash411 2008
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[32] S AnshumanMDeepikaG Sharmila andCMuthukumaranldquoEffect of glucose and phytohaemagglutinin (PHA) richPhaseo-lus vulgaris extract on growth and protein synthesis of pharma-ceutically important cyanobacteriaNostoc ellipsosporumNCIM2786rdquo Journal of Genetic Engineering and Biotechnology vol 11no 1 pp 33ndash37 2013
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[39] M Plaza M Herrero A Alejandro Cifuentes and E IbanezldquoInnovative natural functional ingredients from microalgaerdquoJournal of Agricultural and Food Chemistry vol 57 no 16 pp7159ndash7170 2009
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[60] G E Fogg ldquoThe ecological significance of extracellular prod-ucts of phytoplankton photosynthesisrdquo Botanica Marina vol26 no 1 pp 3ndash14 1983
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[64] H K Madhyastha S Sivashankari and T M Vatsala ldquoC-phycocyanin from Spirulina fussiformis exposed to blue lightdemonstrates higher efficacy of in vitro antioxidant activityrdquoBiochemical Engineering Journal vol 43 no 2 pp 221ndash2242009
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[73] P-F Ip and F Chen ldquoPeroxynitrite and nitryl chloride enhanceastaxanthin production by the green microalga Chlorella zofin-giensis in heterotrophic culturerdquo Process Biochemistry vol 40no 11 pp 3595ndash3599 2005
[74] D L Alonso E-H Belarbi J M Fernandez-Sevilla JRodrıguez-Ruiz and E M Grima ldquoAcyl lipid compositionvariation related to culture age and nitrogen concentration incontinuous culture of the microalga Phaeodactylum tricornu-tumrdquo Phytochemistry vol 54 no 5 pp 461ndash471 2000
[75] W Schmidell A U Lima E Aquarone and W BorzaniBiotecnologia Industrial Volume 2 Edgard Blucher Sao PauloBrazil 2001
[76] R R L Guillard ldquoCulture of phytoplankton for feeding marineinvertebratesrdquo in Culture of Marine Invertebrate Animals W LSmith and M H Chanley Eds pp 29ndash60 Plenum New YorkNY USA 1975
[77] R Pangestuti and S-K Kim ldquoBiological activities and healthbenefit effects of natural pigments derived from marine algaerdquoJournal of Functional Foods vol 3 no 4 pp 255ndash266 2011
[78] K Skjanes C Rebours and P Lindblad ldquoPotential for greenmicroalgae to produce hydrogen pharmaceuticals and otherhigh value products in a combined processrdquo Critical Reviews inBiotechnology vol 33 no 2 pp 172ndash215 2013
[79] I Rodrıguez-Meizoso L Jaime S Santoyo F J Senorans ACifuentes and E Ibanez ldquoSubcritical water extraction andcharacterization of bioactive compounds from Haematococcuspluvialis microalgardquo Journal of Pharmaceutical and BiomedicalAnalysis vol 51 no 2 pp 456ndash463 2010
[80] M Herrero M Castro-Puyana J A Mendiola and E IbanezldquoCompressed fluids for the extraction of bioactive compoundsrdquoTrends in Analytical Chemistry vol 43 pp 67ndash83 2013
[81] N K Singh and D W Dhar ldquoMicroalgae as second generationbiofuel A reviewrdquo Agronomy for Sustainable Development vol31 no 4 pp 605ndash629 2011
[82] L Brennan and P Owende ldquoBiofuels frommicroalgae towardsmeeting advanced fuel standardsrdquo in Advanced Biofuels andBioproducts JW Lee Ed pp 553ndash599 Springer NewYork NYUSA 2013
[83] A Singh P S Nigam and J D Murphy ldquoRenewable fuels fromalgae an answer to debatable land based fuelsrdquo BioresourceTechnology vol 102 no 1 pp 10ndash16 2011
[84] P Perez-Lopez S Gonzalez-Garcıa R G Ulloa J SineiroG Feijoo and M T Moreira ldquoLife cycle assessment of the
production of bioactive compounds from Tetraselmis suecica atpilot scalerdquo Journal of Cleaner Production vol 64 pp 323ndash3312014
[85] B Subhadra ldquoAlgal biorefinery-based industry an approachto address fuel and food insecurity for a carbon-smart worldrdquoJournal of the Science of Food and Agriculture vol 91 no 1 pp2ndash13 2011
[86] D J Newman and G M Cragg ldquoNatural products as sourcesof new drugs over the 30 years from 1981 to 2010rdquo Journal ofNatural Products vol 75 no 3 pp 311ndash335 2012
[87] H-B Li K-W Cheng C-C Wong K-W Fan F Chen andY Jiang ldquoEvaluation of antioxidant capacity and total phenoliccontent of different fractions of selected microalgaerdquo FoodChemistry vol 102 no 3 pp 771ndash776 2007
[88] T M Mata A A Martins and N S Caetano ldquoMicroalgaefor biodiesel production and other applications a reviewrdquoRenewable and Sustainable EnergyReviews vol 14 no 1 pp 217ndash232 2010
[89] A Gupta and J K Sainis ldquoIsolation of C-phycocyanin fromSynechococcus sp (Anacystis nidulans BD1)rdquo Journal of AppliedPhycology vol 22 no 3 pp 231ndash233 2010
[90] P J Viskari and C L Colyer ldquoRapid extraction of phyco-biliproteins from cultured cyanobacteria samplesrdquo AnalyticalBiochemistry vol 319 no 2 pp 263ndash271 2003
[91] R Bermejo Roman J M Alvarez-Pez F G Acien Fernandezand E Molina Grima ldquoRecovery of pure B-phycoerythrin fromthe microalga Porphyridium cruentumrdquo Journal of Biotechnol-ogy vol 93 no 1 pp 73ndash85 2002
[92] C I Cazzonelli ldquoCarotenoids in nature insights from plantsand beyondrdquo Functional Plant Biology vol 38 no 11 pp 833ndash847 2011
[93] M A Hejazi and R HWijffels ldquoMilking of microalgaerdquo Trendsin Biotechnology vol 22 no 4 pp 189ndash194 2004
[94] S Arad and O Levy-Ontman ldquoRed microalgal cell-wallpolysaccharides biotechnological aspectsrdquo Current Opinion inBiotechnology vol 21 no 3 pp 358ndash364 2010
[95] M Kim J H Yim S-Y Kim et al ldquoIn vitro inhibitionof influenza A virus infection by marine microalga-derivedsulfated polysaccharide p-KG03rdquoAntiviral Research vol 93 no2 pp 253ndash259 2012
[96] Z A Mohamed ldquoPolysaccharides as a protective responseagainst microcystin-induced oxidative stress in Chlorella vul-garis and Scenedesmus quadricauda and their possible signifi-cance in the aquatic ecosystemrdquo Ecotoxicology vol 17 no 6 pp504ndash516 2008
[97] T Tannin-Spitz M Bergman D Van-Moppes S Grossmanand S Arad ldquoAntioxidant activity of the polysaccharide of thered microalga Porphyridium sprdquo Journal of Applied Phycologyvol 17 no 3 pp 215ndash222 2005
[98] J W Prakash M Johnson and S Jeeva ldquoAntimicrobial activityof certain fresh water microalgae from Thamirabarani RiverTamil Nadu South Indiardquo Asian Pacific Journal of TropicalBiomedicine vol 1 supplement no 2 pp S170ndashS173 2011
[99] H M Amaro A C Guedes and F X Malcata ldquoAntimicrobialactivities of microalgae an invited reviewrdquo in Science againstMicrobial Pathogens Communicating Current Research andTechnological Advances A Mendez-Vilas Ed pp 1272ndash12802011
[100] V J Smith A PDesbois and E ADyrynda ldquoConventional andunconventional antimicrobials from fish marine invertebratesand micro-algaerdquo Marine Drugs vol 8 no 4 pp 1213ndash12622010
14 BioMed Research International
[101] M F D J Raposo A M M B de Morais and R M SC de Morais ldquoInfluence of sulphate on the composition andantibacterial and antiviral properties of the exopolysaccharidefrom Porphyridium cruentumrdquo Life Sciences vol 101 no 1-2 pp56ndash63 2014
[102] M F De Jesus Raposo R M S C De Morais and A M M BDe Morais ldquoHealth applications of bioactive compounds frommarine microalgaerdquo Life Sciences vol 93 no 15 pp 479ndash4862013
[103] A Smelcerovic Z Knezevic-Jugovic and Z PetronijevicldquoMicrobial polysaccharides and their derivatives as current andprospective pharmaceuticalsrdquo Current Pharmaceutical Designvol 14 no 29 pp 3168ndash3195 2008
[104] M T Madigan J M Martinko P V Dunlap and D P ClarkMicrobiologia de Brock Artmed Editora 12th edition 2010
[105] M G de Morais J A V Costa P H L Pranke et alldquoDevelopment of a newnanofiber scaffold for usewith stemcellsin a third degree burn animal modelrdquo Burns Oxford vol 40 no8 pp 1650ndash1660 2014
[106] M G de Morais C Stillings R Dersch et al ldquoPreparation ofnanofibers containing the microalga Spirulina (Arthrospira)rdquoBioresource Technology vol 101 no 8 pp 2872ndash2876 2010
[107] D Steffens M Lersch A Rosa et al ldquoA new biomaterialof nanofibers with the microalga Spirulina as scaffolds tocultivate with stem cells for use in tissue engineeringrdquo Journalof Biomedical Nanotechnology vol 9 no 4 pp 710ndash718 2013
[108] C Barrow and F ShahidiMarine Nutraceuticals and FunctionalFoods CRC Press Taylor amp Francis Boca Raton Fla USA2008
[109] M N A Khan J-Y ChoM-C Lee et al ldquoIsolation of two anti-inflammatory and one pro-inflammatory polyunsaturated fattyacids from the brown seaweed Undaria pinnatifidardquo Journal ofAgricultural and Food Chemistry vol 55 no 17 pp 6984ndash69882007
[110] M S Matsui N Muizzuddin S Arad and K MarenusldquoSulfated polysaccharides from redmicroalgae have antiinflam-matory properties in vitro and in vivordquo Applied Biochemistryand Biotechnology vol 104 no 1 pp 13ndash22 2003
[111] V B Bhat and K M Madyastha ldquoScavenging of peroxynitriteby phycocyanin and phycocyanobilin from Spirulina platensisprotection against oxidative damage to DNArdquo Biochemical andBiophysical Research Communications vol 285 no 2 pp 262ndash266 2001
[112] I A Schepetkin and M T Quinn ldquoBotanical polysaccharidesmacrophage immunomodulation and therapeutic potentialrdquoInternational Immunopharmacology vol 6 no 3 pp 317ndash3332006
[113] J K Park Z-H Kim C G Lee et al ldquoCharacterization andimmunostimulating activity of a water-soluble polysaccharideisolated from Haematococcus lacustrisrdquo Biotechnology and Bio-process Engineering vol 16 no 6 pp 1090ndash1098 2011
[114] S Guzman A Gato M Lamela M Freire-Garabal and J MCalleja ldquoAnti-inflammatory and immunomodulatory activitiesof polysaccharide from Chlorella stigmatophora and Phaeo-dactylum tricornutumrdquo Phytotherapy Research vol 17 no 6 pp665ndash670 2003
[115] E Ryckebosch C Bruneel R Termote-Verhalle K Goiris KMuylaert and I Foubert ldquoNutritional evaluation of microalgaeoils rich in omega-3 long chain polyunsaturated fatty acids as analternative for fish oilrdquo Food Chemistry vol 160 pp 393ndash4002014
[116] P Zhao Z Zang X Xie A Huang and G Wang ldquoTheinfluence of different flocculants on the physiological activityand fucoxanthin production of Phaeodactylum tricornutumrdquoProcess Biochemistry vol 49 no 4 pp 681ndash687 2014
[117] D Moreau C Tomasoni C Jacquot et al ldquoCultivated microal-gae and the carotenoid fucoxanthin from Odontella auritaas potent anti-proliferative agents in bronchopulmonary andepithelial cell linesrdquo Environmental Toxicology and Pharmacol-ogy vol 22 no 1 pp 97ndash103 2006
[118] H Maeda M Hosokawa T Sashima K Funayama and KMiyashita ldquoFucoxanthin from edible seaweed Undaria pinnati-fida shows antiobesity effect through UCP1 expression in whiteadipose tissuesrdquo Biochemical and Biophysical Research Commu-nications vol 332 no 2 pp 392ndash397 2005
[119] J E Piero Estrada P Bermejo Bescos and A M Villar delFresno ldquoAntioxidant activity of different fractions of Spirulinaplatensis protean extractrdquo IL Farmaco vol 56 no 5ndash7 pp 497ndash500 2001
[120] S-M Kang S-J Heo K-N Kim S-H Lee and Y-JJeon ldquoIsolation and identification of new compound 2710158401015840-phloroglucinol-661015840-bieckol from brown algae Ecklonia cavaand its antioxidant effectrdquo Journal of Functional Foods vol 4no 1 pp 158ndash166 2012
[121] HHAbdEl-Baky F K El Baz andG S El-Baroty ldquoProductionof phenolic compounds from Spirulinamaximamicroalgae andits protective effectsrdquoAfrican Journal of Biotechnology vol 8 no24 pp 7059ndash7067 2009
[122] A C Guedes H M Amaro and F X Malcata ldquoMicroalgae assources of carotenoidsrdquoMarineDrugs vol 9 no 4 pp 625ndash6442011
[123] G L Renju G M Kurup and K C H Saritha ldquoEffect oflycopene from Chlorella marina on high cholesterol-inducedoxidative damage and inflammation in ratsrdquo Inflammopharma-cology vol 22 no 1 pp 45ndash54 2014
[124] G L Renju G M Kurup and C H S Kumari ldquoAnti-inflammatory activity of lycopene isolated from Chlorellamarina onType II Collagen induced arthritis in SpragueDawleyratsrdquo Immunopharmacology and Immunotoxicology vol 35 no2 pp 282ndash291 2013
[125] C Vılchez E Forjan M Cuaresma F Bedmar I Garbayo andJ M Vega ldquoMarine carotenoids biological functions andcommercial applicationsrdquo Marine Drugs vol 9 no 3 pp 319ndash333 2011
[126] G Richardson ldquoBeyond eye healthrdquo Life Extension Magazine2011 httpwwwleforgMagazine20117Beyond-Eye-HealthPage-01
[127] M Abidov Z Ramazanov R Seifulla and S Grachev ldquoTheeffects of Xanthigen in the weight management of obesepremenopausal women with non-alcoholic fatty liver diseaseand normal liver fatrdquo Diabetes Obesity and Metabolism vol 12no 1 pp 72ndash81 2010
[128] H M Ragap R H Khalil and H HMutawie ldquoImmunostimu-lant effects of dietary Spirulina platensis on tilapia Oreochromisniloticusrdquo Journal of Applied Pharmaceutical Science vol 2 no2 pp 26ndash31 2012
[129] W Xu Z Gao Z Qi M Qiu J-Q Peng and R Shao ldquoEffect ofdietary chlorella on the growth performance and physiologicalparameters of gibel carp Carassius auratus gibeliordquo TurkishJournal of Fisheries and Aquatic Sciences vol 14 no 1 pp 53ndash572014
[130] P Amaninejad H Emadi M Ematiazjoo et al ldquoEffects ofDunaliella microalgae (Dunaliella salina) on different level of
BioMed Research International 15
IgM Immunoglobulin in rainbow trout (Oncrohynchusmykiss)rdquoGlobal Journal of Biodiversity Science and Management vol 3no 2 pp 237ndash242 2013
[131] V Mimouni L Ulmann V Pasquet et al ldquoThe potential ofmicroalgae for the production of bioactive molecules of phar-maceutical interestrdquoCurrent Pharmaceutical Biotechnology vol13 no 15 pp 2733ndash2750 2012
[132] S M Tosh and S Yada ldquoDietary fibres in pulse seeds and frac-tions characterization functional attributes and applicationsrdquoFood Research International vol 43 no 2 pp 450ndash460 2010
[133] H M Amaro R Barros A C Guedes I Sousa-Pinto and FXMalcata ldquoMicroalgal compoundsmodulate carcinogenesis inthe gastrointestinal tractrdquo Trends in Biotechnology vol 31 no 2pp 92ndash98 2013
[134] S S M Mostafa ldquoMicroalgal biotechnology prospects andapplicationsrdquo in Plant Science chapter 12 pp 275ndash314 InTech2012
[135] L Custodio T Justo L Silvestre et al ldquoMicroalgae of dif-ferent phyla display antioxidant metal chelating and acetyl-cholinesterase inhibitory activitiesrdquoFoodChemistry vol 131 no1 pp 134ndash140 2012
[136] C-CHu J-T Lin F-J Lu F-P Chou andD-J Yang ldquoDetermi-nation of carotenoids in Dunaliella salina cultivated in Taiwanand antioxidant capacity of the algal carotenoid extractrdquo FoodChemistry vol 109 no 2 pp 439ndash446 2008
23 Chlorella Spirulina and Chlorella represent the majorityof themicroalgal biomass market with an annual productionof 3000 and 4000 tons respectively [38] Chlorella sp isa eukaryotic genus of green unicellular microalgae thatbelongs to the Chlorophyta group (Figure 3) [39]
This microalga was discovered by the Japanese tradi-tional consumers of algae who usually enjoy it and use itas a food supplement The microalga Chlorella is rich inchlorophyll proteins polysaccharides vitamins mineralsand essential amino acids This microalga is 53 (ww)protein 23 (ww) carbohydrate 9 (ww) lipids and 5(ww) minerals and oligoelements [22]
These nutrient concentrations can be varied by manipu-lation of culture conditions The biomass of this microalga isalso rich in B complex vitamins especially B12 which arevital in the formation and regeneration of blood cells LikeSpirulina Chlorella has a GRAS certificate issued by the FDAand can thus be used as a food without risk to human healthwhen grown in a suitable environment with proper hygieneand good manufacturing practices [22 40]
Chlorella contains bioactive substances with medicinalproperties Experimental studies with Chlorella demon-strated their antitumor anticoagulant antibacterial antiox-idant and antihiperlipidemia effects in addition to a hepato-protective property and the immunostimulatory activity ofenzymatic protein hydrolyzate [39 41ndash44]
Many antioxidant compounds may be responsible forChlorella functional activities Antioxidants such as lutein 120572-carotene 120573-carotene ascorbic acid and 120572-tocopherol whichare active against free radicals were identified Some of thesecompounds not only are important as natural colorants oradditives but also may be useful in reducing the incidence ofcancer and in the prevention ofmacular degeneration [39 45](Table 4)
The most important bioactive compound in Chlorellais 120573-13 glucan an active immunostimulator that reducesfree radicals and blood cholesterol The efficacy of thiscompound against gastric ulcers sores and constipation hasbeen reported It also has been demonstrated to have preven-tive action against atherosclerosis and hypercholesterolemia
BioMed Research International 5
Table 4 Bioactive compounds extracted from the microalgae of the Chlorella genus
as well as antitumor activity [46] Chlorella is produced bymore than 70 companies Taiwan Chlorella ManufacturingCo (Taipei Taiwan) is the worldrsquos largest producer ofChlorella with over 400000 tons of biomass producedper year (httpwwwtaiwanchlorellacomindexphp) Sig-nificant production also occurs in Klotze (Germany) (80ndash100 t yrminus1 of dry biomass) [47]
24 Dunaliella Dunaliella is a green unicellular halotol-erant microalga that belongs to the Chlorophyceae group(Figure 4) This microalga is widely studied due to its tol-erance of extreme habitat conditions physiological aspectsand its many biotechnological applications Dunaliella is asource of carotenoids glycerol lipids and other bioactivecompounds such as enzymes and vitamins [48 49]
This microalga is a major source of natural 120573-caroteneable to produce up to 14 of its dry weight under conditionsof high salinity light and temperature as well as nutrientlimitation [50] In addition to 120573-carotene this microalgais rich in protein and essential fatty acids which can beconsumed safely as evidenced by GRAS recognition [22]Table 5 presents some compounds that have been extractedfrom microalgae of the Dunaliella genus
Compounds in the Dunaliella biomass have various bio-logical activities such as antioxidant antihypertensive bron-chodilatory analgesic muscle relaxant hepatoprotective andantiedemal properties The microalgal biomass can also be
used directly in food and pharmaceutical formulations [2251]
Chang et al [52] showed that Dunaliella cells containedantibiotic substances According to these authors the crudeextract of this microalga strongly inhibited the growthof Staphylococcus aureus Bacillus cereus Bacillus subtilisand Enterobacter aerogenes In another study Dunaliellamicroalga also showed antibacterial activity against variousmicroorganisms of importance to the food industry includ-ing Escherichia coli Staphylococcus aureus Candida albicansand Aspergillus niger [49 53]
Under ideal growing conditions Dunaliella can be stim-ulated to produce approximately 400mg of 120573-carotene persquare meter of growing area The cultivation of Dunaliellafor the production of 120573-carotene has been conducted inseveral countries including Australia Israel the USA andChina [54ndash56] An ingredient of Dunaliella with a strongability to stimulate cell proliferation and improve the energymetabolism of the skin was released by Pentapharm (BaselSwitzerland) [57] New pilot plants are under development inIndia Chile Mexico Cuba Iran Taiwan Japan Spain andKuwait [50]
3 Cultivation Conditions
The conditions for microalgal cultivation are important fac-tors that influence the metabolism of these microorganismsthus directing the synthesis of specific compounds of interestSeveral researchers have noted the influence of incubationtemperature the pH of themedium the period of cultivationaswell as salinity light intensity andmediumconstituents onthe synthesis of antimicrobial agents [58]
31 pH Temperature and Luminescence pH adjustments arethe primary measures used to prevent contamination bymicroorganisms such as other microalgae species pH con-trol is also essential for effective absorption of the compo-nents of the culture medium because it directly affects theavailability of various chemical elements [59] The reductionof some nutrients in the culturemedium can lead the produc-ing of specific biocompounds The difficulty of consuminga nitrogen source for example can lead microalgae to shiftyourmetabolism for lipids or carbohydrates production [60]
Light is an indispensable factor for photosynthesis caus-ing the cells to reproduce and thereby increasing the cell
6 BioMed Research International
Table 5 Bioactive compounds extracted from the microalgae of the Dunaliella genus
concentration [61] The illuminance also influences the bio-chemical composition of the biomass [62] The fatty acidcontent can be reducedwith increasing light incidenceThis isbecause lipids are the major components of chloroplasts andthe increased light energy demand greater activity of chloro-plasts [63] Studies also show the influence of illuminanceon the microalgae antioxidants According to Madhyastha[64] the application of blue light in the cultivation of themicroalga Spirulina fusiformis through a phenomenon wherethe microalgae cells alter the sequence of amino acids withcysteine repeats enhanced the antioxidant capacity
One of the most important factors for the growth of allliving organisms is the temperature The specific growth rateof the microalgae is directly correlated with the gross rate ofCO2
fixationO2
production (photosynthesis) and the respi-ration rate Photosynthesis and respiration are temperature-dependent with the respiration rate increasing exponentiallywith temperature [65] Temperature has a great influenceon the production of biomass proteins lipids and phenoliccompounds from microalgae The optimum temperature forcultivation of microalgae is 35ndash37∘C [66] In studies con-ducted by Noaman [58] that were performed to verifywhich culture conditions stimulated the greatest produc-tion of antimicrobial agents by the microalga Synechococcusleopoliensis it was observed that a temperature of 35∘C andpH 8 produced a maximum concentration of this bioactivecompound
32 Bioreactors Microalgae have attracted much interest forproduction of bioactive compounds and in order to growand tap the potentials of algae efficient photobioreactors arerequired A good number of photobioreactors can be used inproduction of various algal products [67] Innovative culti-vation systems andmodification of biochemical compositionof microalgae by simple changes in the growth media andcultivation conditions (nutrients light intensity temperaturepH mixing etc) can lead to higher productivity of thetargeted products [68]
Bioreactors can be classified as open or closed Closedphotobioreactors have attracted much interest because theyallow a better control of the cultivation conditions than opensystems One of the major advantages of open ponds is thatthey are easier to construct and operate than most closedsystems [67]
In open systems temperature is a main limiting factoras are variations in solar radiation that lead to low biomassconcentrations However open systems are the most widely
used due to their economic viability Closed systems aregenerally used on a pilot scale for investigating problemsrelated to economic viability Furthermore the use of closedsystems is primarily used for microalgal species that do notgrow in a highly selective medium avoiding contaminationof the cultures [69]
Closed bioreactors can provide high productivity gen-erating greater microalgal biomass per unit time Otheradvantages of the use of closed bioreactors compared withopen systems include the following (i) virtually zero losses inconnection with evaporation (ii) a marked reduction ofproblems related to culture contamination by heterotrophicalgae or othermicroorganisms (iii) ease of biomass collectionprocedures due to smaller volumes of culture medium (iv)greater control of gas exchange between the culture andthe atmosphere (v) a smaller occupied space (vi) a highsurfacevolume ratio which helps to increase the illuminationof the system and (vii) the possibility of obtaining high puritycultures [59]
33 Nutrients The metabolism of microalgae can beautotrophic or heterotrophic The former requires onlyinorganic compounds such as CO
2
salts and solar energythe latter is not photosynthetic requiring an external sourceof organic compounds for use as a nutrient and energy sourceSome photosynthetic species are mixotrophic having theability to perform photosynthesis and use exogenous organicsources simultaneously [70]
Microalgae react to changes in their external environmentwith changes in their intracellular environment Thus themanipulation of the culture conditions or the presence orabsence of nutrients stimulates the biosynthesis of specificcompounds This fact was first referenced by Richmond[71] who changed the composition of Chlorella biomassparticularly in their protein and lipid content by varyingcultivation conditions
Noaman [58] found that leucine combined with citrateor acetate is the sources of nitrogen and carbon that pro-duced higher concentrations of antimicrobial agents in themicroalga Synechococcus leopoliensis Coca et al [72] study-ing the cultivation of Spirulina platensis in a medium sup-plemented with vinasse obtained an increased protein yieldcompared to the unsupplemented culture medium Ip andChen [73] studying the cultivation of Chlorella zofingiensisunder mixotrophic cultivation conditions found that lowconcentrations of nitrate and a high glucose concentrationfavored the production of astaxanthin in this microalga
BioMed Research International 7
Alonso et al [74] studying the influence of nitrogen con-centration in continuous cultivation on lipid concentrationin Phaeodactylum tricornutum noted that there was accu-mulation of saturated and unsaturated fatty acids when thenitrogen source was reduced
Culture media are chemical preparations that are formu-lated to contain the nutrients necessary for the microorgan-isms to multiply andor survive The culture media shouldmeet the nutritional needs of the microorganism assist inprocess control and have a reasonably fixed composition[75]
Among different microalgae variations in the culturemedium are mainly related to the amount of necessary nutri-ents Even so nutritional needs are dependent on environ-mental conditions [59] Microalgae require macronutrientssuch as C N O H P Ca Mg S and K for their growthThe micronutrients that are generally required are Fe MnCu Mo and Co Additionally some species require lowerconcentrations of vitamins in the culture medium [76]
4 Advantages of Using Microalgae to ObtainBioactive Compounds
Microalgae are important sources of bioactive natural sub-stances Many metabolites isolated from these microorgan-isms have shown biological activities and potential healthbenefits [77] Microalgae accumulate specific secondarymetabolites (such as pigments and vitamins) which are highvalue products that have applications in the cosmetic foodor pharmaceutical industries [8 78]
Microalgae live in complex habitats and are subjectedto stress andor extreme conditions such as changes insalinity temperature and nutrients Thus these microorgan-isms must rapidly adapt to new environmental conditions tosurvive and thus produce a great variety of biologically activesecondary metabolites that are not found in other organisms[79] Some of the advantages of microalgal cultivation maybe associated with taxonomic diversity the diverse chemicalcomposition the potential for growth in a bioreactor undercontrolled conditions and the ability to produce activesecondary metabolites in response to the stress induced byextreme exposure conditions [39 80]
In addition to their natural characteristics other impor-tant aspects related to microalgae are the use of solar energyand carbon dioxide (CO
2
) and a high growth rate whichcan produce higher yields compared to higher plants Inaddition microalgae can be grown in areas and climates thatare unsuitable for agriculture therefore microalgae do notcompete with arable food production land The possibility ofcontrolling the production of certain bioactive compoundsby manipulation of culture conditions is another advantageof using microalgae [7 81ndash83]
The cultivation of microalgae is a major mechanism forreducing excess carbon dioxide (CO
2
) in the atmosphere bybiofixation in which an industrial process uses a CO
2
-richgas as a carbon source formicroalgal growthThismechanismcontributes to a reduction of the greenhouse effect and globalwarming further reducing the costs of the carbon source
for growth which is the greatest nutrient requirement formicroalgae [13 84]
The cultivation of microalgae is not seasonal they areimportant for food in aquaculture systems and can effectivelyremove pollutants such as nitrogen and phosphorus fromwastewater Moreover they are themost efficient solar energybiomass converters Microalgae cultivation via sunlight-dependent systems contributes to sustainable developmentand natural resource management [13]
The integration of the production process of bioactivemetabolites in a biorefinery is a sustainable means of energyproduction food production and the production of productswith high added value [7] The biorefinery concept based onmicroalgae depends on the efficient use of biomass throughfractionation resulting in several isolated productsThis con-cept encompasses a biorefinery platform which is capable ofoffering a wide variety of different products such as productswith applications in pharmaceuticals medicine food (pro-tein fiber) and biofuels [7 85] These benefits contribute tothe economic viability of microalgal production [7 8]
5 Bioactive Compounds
Bioactive compounds are physiologically active substanceswith functional properties in the human body There is greatenthusiasm for the development and manufacture of variousbiocompounds that can potentially be used as functionalingredients such as carotenoids phycocyanins polyphenolsfatty acids and polyunsaturated compounds [16]
An interest in the production of bioactive compoundsfrom natural sources has recently emerged driven by agrowing number of scientific studies that demonstrate thebeneficial effects of these compounds on health [80] Naturalproducts are important in the search for new pharmaco-logically active compounds In general they play a role indrug discovery for the treatment of human diseases [86]Many clinically viable and commercially available drugs withantitumor and antiinfective activity originated as naturalproducts
Microalgae are a natural source of interesting biocom-pounds Microalgae are known to produce various therapeu-tically effective biocompounds that can be obtained from thebiomass or released extracellularly into the medium [11]These microorganisms contain many bioactive compoundssuch as proteins polysaccharides lipids vitamins enzymessterols and other high-value compounds with pharmaceu-tical and nutritional importance that can be employed forcommercial use [13]
51 Compounds with Antioxidant Function Oxidative dam-age caused by reactive oxygen species to lipids proteins andnucleic acids can cause many chronic diseases such as heartdisease atherosclerosis cancer and aging Epidemiologicalstudies have demonstrated an inverse association between theintake of fruits and vegetables and mortality from diseasessuch as cancer This phenomenon can be attributed to theantioxidant activity of these foods [87]
8 BioMed Research International
Microalgal biomass is considered a rich natural source ofantioxidants with potential applications in food cosmet-ics and medicine [87] Antioxidant compounds such asdimethylsulfoniopropionate and mycosporine amino acidswere isolated frommicroalgae and are potent chemical block-ers ofUV radiation [88] In addition to these compounds pig-ments lipids and polysaccharides with antioxidant activitycan also be found in microalgal biomass
Carotenoids and phycocyanins are the pigments mostused in scientific research C-phycocyanin (C-PC) is a bluephotosynthetic pigment that belongs to the group of phyco-biliproteins found in large quantities in the cyanobacteriaRhodophyta and Cryptophyte [89] Phycocyanin has appli-cations as a nutrient and natural food colorants and cosmet-ics It is usually extracted from the biomass of Spirulina [90]and Porphyridium cruentum [91] and Synechococcus [89]
Among the carotenoid compounds 120573-carotene andastaxanthin are prominent These compounds have appli-cation in the food and pharmaceutical industries becauseof their antioxidant properties and pigmentation ability Inmicroalgal metabolism they protect photosynthetic tissuesagainst damage caused by light and oxygen [92] Dunaliellasalina is a microalga recognized as a major biological sourceof 120573-carotene pigment producing more than 14 in drybiomass [46] H pluvialis is a source of the pigment astax-anthin producing 1ndash8 of astaxanthin as dry biomass [93]
Polysaccharides represent a class of high value-addedcomponents with applications in food cosmetics fabrics sta-bilizers emulsifiers and medicine [94] Microalgal polysac-charides contain sulphate esters are referred to as sulfatedpolysaccharides and possess unique medical applicationsThe basic mechanism of therapeutic action is based on thestimulation of macrophages and modulation The biologicalactivity of sulfur polysaccharides is linked to their sugarcomposition position and degree of sulfation [95] Amongthe microalgae capable of producing these compounds areChlorella vulgaris Scenedesmus quadricauda [96] and Por-phyridium sp [97]
52 Compounds with Antimicrobial Activity The importanceof discovering new compounds with antimicrobial activityis driven by the development of antibiotic resistance inhumans due to constant clinical use of antibioticsMicroalgaeare an important source of antibiotics with a broad andefficient antibacterial activity [11] The antimicrobial activityof these microorganisms is due to the ability to synthesizecompounds such as fatty acids acrylic acids halogenatedaliphatic compounds terpenoids sterols sulfur-containingheterocyclic compounds carbohydrates acetogenins andphenols [98]
The antimicrobial activity of extracts from microalgae isrelated to its lipid composition The antimicrobial action ofmicroalgae is also noteworthy because of the potential toproduce compounds such as 120572- and 120573-ionone 120573-cyclocitralneophytadiene and phytol [99] Microalgae antimicrobialactivity against human pathogens such as Escherichia coliPseudomonas aeruginosa Staphylococcus aureus and Staphy-lococcus epidermidis has been attributed to 120574-linolenic acid
The mechanism of action of fatty acids affects variousstructures in microorganisms however cell membranes arethe most impacted Membrane damage most likely leadsto a loss of internal substances from the cells and theentry of harmful components reduces nutrient absorption inaddition to inhibiting cellular respiration The ability of fattyacids to interfere with bacterial growth depends on boththeir chain length and the degree of unsaturation Fatty acidswith more than 10 carbon atoms apparently induce lysis ofbacterial protoplasts [99]
Microbial polysaccharides and other biological com-pounds have antiviral and antimicrobial action Microalgaeproduce extracellular sulfated polysaccharide (EPS) withacidic characteristics that has a potential as a therapeuticagent [101] Highly sulfated antiviral polysaccharides fromseveral species of microalgae consist mainly of xylose glu-cose and galactose The EPS sulfate groups determine somecharacteristics of polysaccharides it has been found thathigher sulphate contents induced higher antiviral activities[94 101] The inhibitory effect of polysaccharides of microal-gal origin is due to viral interactions or positive charges onthe cell surface thereby preventing penetration of the virusinto host cells [99]
The cyanobacterium Spirulina (Arthrospira) can producesulfated polysaccharides that have already found applicationsas antiviral agents both in vivo and in vitro [102] Eukaryoticmicroalgae such as Chlorella sp and Dunaliella sp produceand secrete polysaccharides at relatively high levels [17] Theantibacterial ability of Spirulina has been correlated withtheir volatile composition resulting in the identification of15 elements which constitutes 96 of total compounds Themajor volatile components produced by Spirulina consist ofheptadecane (40) and tetradecane (35) [39]
Some studies have reported that sulfated polysaccharidesderived from microalgae inhibit viral infection such asencephalomyocarditis virus Herpes simplex virus types 1and 2 (HSV1 HSV2) human immunodeficiency virus (HIV)hemorrhagic septicemia in salmonid virus swine fever virusand varicella virus [99 103] Carrageenan is a sulfatedpolysaccharide that can directly bind to human papillo-mavirus to inhibit not only the viral adsorption process butalso the input and subsequent process of the uncoating of thevirus [101]
53 Compounds with Anti-Inflammatory Action Inflam-mation is an immediate reaction to a cell or tissueinjury caused by noxious stimuli such as toxins andpathogens In this situation the body recognizes theagents responsible for the attack and attempts to neu-tralize them as quickly as possible Inflammation causesredness swelling heat and pain usually located at thesite of infection [104] Ingestion of anti-inflammatory com-pounds enhances the bodyrsquos immune response and helpsto prevent disease and aids the healing process Microal-gae produce several anti-inflammatory compounds in their
BioMed Research International 9
biomass that may exert a protective function in the bodywhen consumed as food or used as pharmaceuticals andcosmetics
Because of its anti-inflammatory capabilities microalgalbiomass is being considered for applications in tissue engi-neering for the development of scaffolds for use in reconsti-tution of organs and tissues [105 106] This is an importantapplication for humans especially in patients with burnsin which the skin was completely lost [107] Among themost important microalgal compounds with such prop-erties are long-chain polyunsaturated fatty acids (PUFAs)[108 109] sulfurized polysaccharides [110] and pigments[111]
Many microalgal polysaccharides possess the ability tomodulate the immune system through the activation ofmacrophage functions and the induction of reactive oxy-gen species (ROS) nitric oxide (NO) and various othertypes of cytokineschemokines [112] Macrophages are ableto regulate several innate responses and secrete cytokinesand chemocytokines that serve as signals for immune andinflammatory molecular reactions [113] Sulfur polysaccha-rides with anti-inflammatory activity can be applied inskin treatments inhibiting the migration and adhesion ofpolymorphonuclear leukocytes [110] Guzman et al [114]studied the anti-inflammatory capacity of the microalgaChlorella stigmatophora and Phaeodactylum tricomutum andconcluded that bothmicroalgae showed positive responses inthe test of paw edema by carrageenan
The PUFAs especially 1205963 and 1205966 as eicosapentaenoic(EPA) docosahexaenoic (DHA) and arachidonic (AA) acidshave been applied in the treatment of chronic inflammationsuch as rheumatism and skin diseases [108] Ryckebosch etal [115] evaluated the nutritional value of the total lipidsextracted from different PUFAs produced by microalgae Inthis study the microalgae IsochrysisNannochloropsis Phaeo-dactylum Pavlova and Thalassiosira produced 1205963 PUFA asan alternative to fish oil in food
Among the pigments with anti-inflammatory activityfucoxanthin carotenoid found in diatoms [116 117] is capableof stimulating apoptosis in human cancer cells [118] A phy-cocyanin found in cyanobacteria has an anti-inflammatoryactivity that occurs through the inhibition of histaminerelease [111 119]
54 Compounds with Potentiality over Degenerative Dis-eases In humans the oxidation reactions driven by reactiveoxygen species (ROS) can lead to irreversible damage tocellular components including lipids proteins and DNAdegradation andor mutation Consequently this damagecan lead to several syndromes such as cardiovascular dis-ease some cancers and the degenerative diseases of aging[120]
Chronic age-related diseases involve oxidative stress andinflammation and their consequences Chronic inflammationplays a significant role in the mediation of neurodegenerativediseases such as Parkinsonrsquos disease Alzheimerrsquos diseasemultiple sclerosis acquired immunodeficiency syndrome(AIDS) and dementia complex [77]
Natural pigments derived from microalgae (NPs) haveneuroprotective properties being valuable sources as func-tional ingredients in foods and pharmaceutical products thatshow efficient action in the treatment andor prevention ofneurodegenerative diseases Vitamin E has preventive effectsfor many diseases such as atherosclerosis and heart diseaseas well as neurodegenerative diseases such as multiplesclerosis [77]
Carotenoids have great potential benefits to humanhealth including the treatment of degenerative diseases suchas macular degeneration and cataract development Thesecompounds act as antioxidants reducing oxidative damageby ROS Studies indicated that increased intake of phenolsdecreased the occurrence of degenerative diseases Phenoliccompounds from microalgae with the potential to fight freeradicals have been reported [121]
Dunaliella salina is a natural source of 120573-carotene whichproduced a reduced risk of cancer and degenerative diseasesin humans Lutein is effective against various diseases includ-ing cataracts and macular degeneration and in the earlystages of atherosclerosis Extracts of Chlorella sp containing120573-carotene and lutein significantly prevented the cognitivedisability that accompanies Alzheimerrsquos disease in rats It wasalso reported that lutein extracted from Chlorella reducedthe incidence of cancer Likewise carotenoids extractedfrom Chlorella ellipsoidea and Chlorella vulgaris inhibited thegrowth of colon cancer [122] A lycopene extracted fromthe microalgae Chlorella marina significantly reduced theproliferation of prostate cancer inmice [123]This compoundalso reduced total cholesterol and low-density lipoprotein(LDL) levels [123] and improved rheumatoid arthritis [124]
Low plasma levels of lutein have also been associatedwith an increased tendency ofmyocardial infarction whereashigh intake of lutein was related to a decreased risk ofstroke In addition high levels of carotenoids with provi-tamin A activity including 120572-carotene 120573-carotene and 120573-cryptoxanthin have been associated with reduction in therisk of angina pectoris Macular degeneration the lead-ing cause of irreversible vision loss has also been associ-ated with very low consumption of lutein and zeaxanthin[125]
Scientific findings indicate astaxanthin for multimodalintervention formany forms of degenerative diseases includ-ing cardiovascular diseases cancer metabolic syndromecognitive impairment age-related immune dysfunctionstomach and ocular diseases (macular degeneration cataractglaucoma diabetic retinopathy and retinitis pigmentosa)and skin damage [126] High levels of lycopene in plasmaand tissues were inversely related to coronary heart diseasemyocardial infarction and the risk of atherosclerosis [125]
55 Compounds withHealth Promoting Function The impor-tance of microalgae as sources of functional ingredients hasbeen recognized because of their beneficial health effectsNatural pigments are valuable sources of bioactive com-pounds These pigments have various beneficial biologicalactivities such as antioxidant anticancer anti-inflammatoryantiobesity antiangiogenic and neuroprotective action and
10 BioMed Research International
are indicated for the treatment or prevention of severalchronic diseases [77]
The antioxidant potential of carotenoid pigments andtheir ability to prevent cancer aging atherosclerosis coro-nary heart disease and degenerative diseases have beendescribed 120573-Carotene has higher provitamin A activitywhich is essential for vision and the correct functioning ofthe immune system Astaxanthin is linked to many healthbenefits such as protection against lipid peroxidation age-related macular degeneration reduced atherosclerosis andan increased immune response [102]
Fucoxanthin is considered as a promising dietary andweight loss supplement and for the treatment of obesityClinical studies by Abidov et al [127] demonstrated the effectof ldquoxanthigenrdquo a fucoxanthin based antiobesity supplementFurthermore fucoxanthinmay be useful for the prevention ofbone diseases such as osteoporosis and rheumatoid arthritisIt has also been reported to be effective for the therapeutictreatment of diabetic diseases suppressing insulin and hyper-glycemia [77]
Microalgae proteins are of great interest as a source ofbioactive peptides due to their therapeutic potential in thetreatment of various diseases [7] Proteins peptides andamino acids have functions that contribute to health benefitsThese compounds can include growth factors hormones andimmunomodulators and can help to replace damaged tissuesin addition to providing nutritional benefits Microalgaesuch as Chlorella and Spirulina (Arthrospira) may be usedas nutraceuticals or included in functional foods to preventdiseases and damage to cells and tissues due to their richprotein content and amino acid profile [102]
The antimicrobial action of certain enzymes (eglysozyme) and immunoglobulins has been reported andrecommended for people with different diseases (egCrohnrsquos disease) due to the existence of formulations withpeptides and free amino acids Studies of the healtheffects of lysozyme have been reported in the microalgaeSpirulina platensis [128] Chlorella [129] and Dunaliellasalina [130] Spirulina (Arthrospira) and Chlorella biomasspills are marketed as is ldquoHawaiian Spirulina Pacificardquo(httpspirulinagreennutritionalscomau) Other proteinscan also increase the production of cholecystokinin involvedin appetite suppression and the reduction of LDL-cholesterolProtein peptides from Chlorella have a potential as dietarysupplements for the prevention of oxidative stress-relateddiseases such as atherosclerosis coronary heart disease andcancer [39]
The essential fatty acids 120596-3 and 120596-6 in particular areimportant for the integrity of tissues 120574-Linolenic acid hastherapeutic applications in cosmetics to revitalize the skinand thus slow aging Linoleic and linolenic acids are essentialnutrients for the immune system and other related tissueregeneration processes Linoleic acid is also used for thetreatment of hyperplasia of the skin [102]
The most studied microalgal lipid compounds are thepolyunsaturated fatty acids (PUFAs) docosahexaenoic acid(120596-3 C226) (DHA) eicosapentaenoic acid (C20 120596-35)(EPA) and arachidonic acid (120596-6 C204) (ARA) Studies haveshown that dietary120596-3 PUFAs have a protective effect against
atherosclerotic heart disease [131] DHA and EPA showed theability to reduce problems associated with strokes and arthri-tis besides reducing hypertension lipid content (a decreasein triglycerides and an increase of HDL) and acting asanti-inflammatory agents DHA is also important in thedevelopment and function of the nervous system Further-more ARA and EPA are platelet aggregators vasoconstric-tors and vasodilators and have antiaggregative action on theendothelium as well as chemostatic activity in neutrophils[102]
Other lipid compounds with interesting bioactive prop-erties are the microalgal sterols Phytosterols have demon-strated reduction of total cholesterol (LDL) in humans byinhibiting its absorption from the intestine [50] Polysac-charides can be considered as dietary fibers associatedwith different physiological effects Insoluble fiber (cellulosehemicellulose and lignin) mainly promotes the movementof material through the digestive system thereby improvinglaxation and increasing satietyThey can also be considered asprebiotics because they promote the growth of gutmicrofloraincluding probiotic species Soluble fiber (oligosaccharidespectins and 120573-glucans) may reduce cholesterol and regulateblood glucose [7 132]
6 Conclusion
The proven ability of microalgae to produce bioactive com-pounds places these microorganisms in the biotechnologicalspotlight for applications in various areas of study especiallyin the life sciencesThe production ofmicroalgal metaboliteswhich stimulate defense mechanisms in the human bodyhas spurred intense study of the application of microalgalbiomass in various foods and pharmacological and medicalproducts There is obviously a need for further study of theidentified compounds and their activities in the treatmentand prevention of various diseases in addition to an ongoingsearch for other as yet undetected metabolites
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgment
The authors thank the National Counsel of Technologicaland Scientific Development (CNPq) for the Productivityin Technological Development and Innovative ExtensionScholarship
References
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[2] A A El Gamal ldquoBiological importance of marine algaerdquo SaudiPharmaceutical Journal vol 18 no 1 pp 1ndash25 2010
BioMed Research International 11
[3] I Moreno-Garrido ldquoMicroalgae immobilization current tech-niques and usesrdquo Bioresource Technology vol 99 no 10 pp3949ndash3964 2008
[4] R-B Volk and F H Furkert ldquoAntialgal antibacterial andantifungal activity of two metabolites produced and excretedby cyanobacteria during growthrdquoMicrobiological Research vol161 no 2 pp 180ndash186 2006
[5] R-B Volk ldquoA newly developed assay for the quantitativedetermination of antimicrobial (anticyanobacterial) activity ofboth hydrophilic and lipophilic test compounds without anyrestrictionrdquoMicrobiological Research vol 163 no 2 pp 161ndash1672008
[6] D F Smee K W Bailey M-H Wong et al ldquoTreatment ofinfluenza A (H1N1) virus infections in mice and ferrets withcyanovirin-Nrdquo Antiviral Research vol 80 no 3 pp 266ndash2712008
[7] E Ibanez and A Cifuentes ldquoBenefits of using algae as naturalsources of functional ingredientsrdquo Journal of the Science of Foodand Agriculture vol 93 no 4 pp 703ndash709 2013
[8] G Markou and E Nerantzis ldquoMicroalgae for high-valuecompounds and biofuels production a review with focus oncultivation under stress conditionsrdquo Biotechnology Advancesvol 31 no 8 pp 1532ndash1542 2013
[9] R Harun M Singh G M Forde andM K Danquah ldquoBiopro-cess engineering ofmicroalgae to produce a variety of consumerproductsrdquo Renewable and Sustainable Energy Reviews vol 14no 3 pp 1037ndash1047 2010
[10] C Kolympiris N Kalaitzandonakes and D Miller ldquoPublicfunds and local biotechnology firm creationrdquo Research Policyvol 43 no 1 pp 121ndash137 2014
[11] S Bhagavathy P Sumathi and I Jancy Sherene Bell ldquoGreenalgae Chlorococcum humicola-a new source of bioactive com-pounds with antimicrobial activityrdquo Asian Pacific Journal ofTropical Biomedicine vol 1 no 1 pp S1ndashS7 2011
[12] A M F Palavra J P Coelho J G Barroso et al ldquoSupercrit-ical carbon dioxide extraction of bioactive compounds frommicroalgae and volatile oils from aromatic plantsrdquo Journal ofSupercritical Fluids vol 60 pp 21ndash27 2011
[13] I Priyadarshani and B Rath ldquoCommercial and industrialapplications of micro algaemdasha reviewrdquo Journal of Algal BiomassUtilization vol 3 no 4 pp 89ndash100 2012
[14] JW Blunt B R CoppM H GMunro P T Northcote andMR Prinsep ldquoMarine natural productsrdquoNatural Product Reportsvol 23 no 1 pp 26ndash78 2006
[15] A M S Mayer and M T Hamann ldquoMarine pharmacologyin 2001-2002 marine compounds with anthelmintic antibacte-rial anticoagulant antidiabetic antifungal anti-inflammatoryantimalarial antiplatelet antiprotozoal antituberculosis andantiviral activities affecting the cardiovascular immune andnervous systems and other miscellaneous mechanisms ofactionrdquo Comparative Biochemistry and Physiology Part C Toxi-cology amp Pharmacology vol 140 no 3-4 pp 265ndash286 2005
[16] M Plaza S Santoyo L Jaime et al ldquoScreening for bioactivecompounds from algaerdquo Journal of Pharmaceutical and Biomed-ical Analysis vol 51 no 2 pp 450ndash455 2010
[17] I Rodrıguez-Meizoso L Jaime S Santoyo et al ldquoPressurizedfluid extraction of bioactive compounds from Phormidiumspeciesrdquo Journal of Agricultural and Food Chemistry vol 56 no10 pp 3517ndash3523 2008
[18] L R Carvalho A Costa-Neves G A A Conserva et alldquoBiologically active compounds from cyano bacteria extracts in
vivo and in vitro aspectsrdquo Brazilian Journal of Pharmacognosyvol 23 no 3 pp 471ndash480 2013
[19] B Nobre FMarcelo R Passos et al ldquoSupercritical carbon diox-ide extraction of astaxanthin and other carotenoids from themicroalga Haematococcus pluvialisrdquo European Food Researchand Technology vol 223 no 6 pp 787ndash790 2006
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extraction of 120574-linolenic acid and other lipids from Arthrospira(Spirulina)maxima comparison with organic solvent extrac-tionrdquo Food Chemistry vol 99 no 1 pp 57ndash63 2006
[21] I Romano M R Bellitti B Nicolaus et al ldquoLipid profilea useful chemotaxonomic marker for classification of a newcyanobacterium in Spirulina genusrdquo Phytochemistry vol 54 no3 pp 289ndash294 2000
[22] J A C Costa and M G Morais ldquoMicroalgae for food produc-tionrdquo in Fermentation Process Engineering in the Food IndustryC R Soccol A Pandey and C Larroche Eds p 486 Taylor ampFrancis 2013
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[25] F S Antelo J A V Costa and S J Kalil ldquoThermal degradationkinetics of the phycocyanin from Spirulina platensisrdquo Biochem-ical Engineering Journal vol 41 no 1 pp 43ndash47 2008
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[79] I Rodrıguez-Meizoso L Jaime S Santoyo F J Senorans ACifuentes and E Ibanez ldquoSubcritical water extraction andcharacterization of bioactive compounds from Haematococcuspluvialis microalgardquo Journal of Pharmaceutical and BiomedicalAnalysis vol 51 no 2 pp 456ndash463 2010
[80] M Herrero M Castro-Puyana J A Mendiola and E IbanezldquoCompressed fluids for the extraction of bioactive compoundsrdquoTrends in Analytical Chemistry vol 43 pp 67ndash83 2013
[81] N K Singh and D W Dhar ldquoMicroalgae as second generationbiofuel A reviewrdquo Agronomy for Sustainable Development vol31 no 4 pp 605ndash629 2011
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production of bioactive compounds from Tetraselmis suecica atpilot scalerdquo Journal of Cleaner Production vol 64 pp 323ndash3312014
[85] B Subhadra ldquoAlgal biorefinery-based industry an approachto address fuel and food insecurity for a carbon-smart worldrdquoJournal of the Science of Food and Agriculture vol 91 no 1 pp2ndash13 2011
[86] D J Newman and G M Cragg ldquoNatural products as sourcesof new drugs over the 30 years from 1981 to 2010rdquo Journal ofNatural Products vol 75 no 3 pp 311ndash335 2012
[87] H-B Li K-W Cheng C-C Wong K-W Fan F Chen andY Jiang ldquoEvaluation of antioxidant capacity and total phenoliccontent of different fractions of selected microalgaerdquo FoodChemistry vol 102 no 3 pp 771ndash776 2007
[88] T M Mata A A Martins and N S Caetano ldquoMicroalgaefor biodiesel production and other applications a reviewrdquoRenewable and Sustainable EnergyReviews vol 14 no 1 pp 217ndash232 2010
[89] A Gupta and J K Sainis ldquoIsolation of C-phycocyanin fromSynechococcus sp (Anacystis nidulans BD1)rdquo Journal of AppliedPhycology vol 22 no 3 pp 231ndash233 2010
[90] P J Viskari and C L Colyer ldquoRapid extraction of phyco-biliproteins from cultured cyanobacteria samplesrdquo AnalyticalBiochemistry vol 319 no 2 pp 263ndash271 2003
[91] R Bermejo Roman J M Alvarez-Pez F G Acien Fernandezand E Molina Grima ldquoRecovery of pure B-phycoerythrin fromthe microalga Porphyridium cruentumrdquo Journal of Biotechnol-ogy vol 93 no 1 pp 73ndash85 2002
[92] C I Cazzonelli ldquoCarotenoids in nature insights from plantsand beyondrdquo Functional Plant Biology vol 38 no 11 pp 833ndash847 2011
[93] M A Hejazi and R HWijffels ldquoMilking of microalgaerdquo Trendsin Biotechnology vol 22 no 4 pp 189ndash194 2004
[94] S Arad and O Levy-Ontman ldquoRed microalgal cell-wallpolysaccharides biotechnological aspectsrdquo Current Opinion inBiotechnology vol 21 no 3 pp 358ndash364 2010
[95] M Kim J H Yim S-Y Kim et al ldquoIn vitro inhibitionof influenza A virus infection by marine microalga-derivedsulfated polysaccharide p-KG03rdquoAntiviral Research vol 93 no2 pp 253ndash259 2012
[96] Z A Mohamed ldquoPolysaccharides as a protective responseagainst microcystin-induced oxidative stress in Chlorella vul-garis and Scenedesmus quadricauda and their possible signifi-cance in the aquatic ecosystemrdquo Ecotoxicology vol 17 no 6 pp504ndash516 2008
[97] T Tannin-Spitz M Bergman D Van-Moppes S Grossmanand S Arad ldquoAntioxidant activity of the polysaccharide of thered microalga Porphyridium sprdquo Journal of Applied Phycologyvol 17 no 3 pp 215ndash222 2005
[98] J W Prakash M Johnson and S Jeeva ldquoAntimicrobial activityof certain fresh water microalgae from Thamirabarani RiverTamil Nadu South Indiardquo Asian Pacific Journal of TropicalBiomedicine vol 1 supplement no 2 pp S170ndashS173 2011
[99] H M Amaro A C Guedes and F X Malcata ldquoAntimicrobialactivities of microalgae an invited reviewrdquo in Science againstMicrobial Pathogens Communicating Current Research andTechnological Advances A Mendez-Vilas Ed pp 1272ndash12802011
[100] V J Smith A PDesbois and E ADyrynda ldquoConventional andunconventional antimicrobials from fish marine invertebratesand micro-algaerdquo Marine Drugs vol 8 no 4 pp 1213ndash12622010
14 BioMed Research International
[101] M F D J Raposo A M M B de Morais and R M SC de Morais ldquoInfluence of sulphate on the composition andantibacterial and antiviral properties of the exopolysaccharidefrom Porphyridium cruentumrdquo Life Sciences vol 101 no 1-2 pp56ndash63 2014
[102] M F De Jesus Raposo R M S C De Morais and A M M BDe Morais ldquoHealth applications of bioactive compounds frommarine microalgaerdquo Life Sciences vol 93 no 15 pp 479ndash4862013
[103] A Smelcerovic Z Knezevic-Jugovic and Z PetronijevicldquoMicrobial polysaccharides and their derivatives as current andprospective pharmaceuticalsrdquo Current Pharmaceutical Designvol 14 no 29 pp 3168ndash3195 2008
[104] M T Madigan J M Martinko P V Dunlap and D P ClarkMicrobiologia de Brock Artmed Editora 12th edition 2010
[105] M G de Morais J A V Costa P H L Pranke et alldquoDevelopment of a newnanofiber scaffold for usewith stemcellsin a third degree burn animal modelrdquo Burns Oxford vol 40 no8 pp 1650ndash1660 2014
[106] M G de Morais C Stillings R Dersch et al ldquoPreparation ofnanofibers containing the microalga Spirulina (Arthrospira)rdquoBioresource Technology vol 101 no 8 pp 2872ndash2876 2010
[107] D Steffens M Lersch A Rosa et al ldquoA new biomaterialof nanofibers with the microalga Spirulina as scaffolds tocultivate with stem cells for use in tissue engineeringrdquo Journalof Biomedical Nanotechnology vol 9 no 4 pp 710ndash718 2013
[108] C Barrow and F ShahidiMarine Nutraceuticals and FunctionalFoods CRC Press Taylor amp Francis Boca Raton Fla USA2008
[109] M N A Khan J-Y ChoM-C Lee et al ldquoIsolation of two anti-inflammatory and one pro-inflammatory polyunsaturated fattyacids from the brown seaweed Undaria pinnatifidardquo Journal ofAgricultural and Food Chemistry vol 55 no 17 pp 6984ndash69882007
[110] M S Matsui N Muizzuddin S Arad and K MarenusldquoSulfated polysaccharides from redmicroalgae have antiinflam-matory properties in vitro and in vivordquo Applied Biochemistryand Biotechnology vol 104 no 1 pp 13ndash22 2003
[111] V B Bhat and K M Madyastha ldquoScavenging of peroxynitriteby phycocyanin and phycocyanobilin from Spirulina platensisprotection against oxidative damage to DNArdquo Biochemical andBiophysical Research Communications vol 285 no 2 pp 262ndash266 2001
[112] I A Schepetkin and M T Quinn ldquoBotanical polysaccharidesmacrophage immunomodulation and therapeutic potentialrdquoInternational Immunopharmacology vol 6 no 3 pp 317ndash3332006
[113] J K Park Z-H Kim C G Lee et al ldquoCharacterization andimmunostimulating activity of a water-soluble polysaccharideisolated from Haematococcus lacustrisrdquo Biotechnology and Bio-process Engineering vol 16 no 6 pp 1090ndash1098 2011
[114] S Guzman A Gato M Lamela M Freire-Garabal and J MCalleja ldquoAnti-inflammatory and immunomodulatory activitiesof polysaccharide from Chlorella stigmatophora and Phaeo-dactylum tricornutumrdquo Phytotherapy Research vol 17 no 6 pp665ndash670 2003
[115] E Ryckebosch C Bruneel R Termote-Verhalle K Goiris KMuylaert and I Foubert ldquoNutritional evaluation of microalgaeoils rich in omega-3 long chain polyunsaturated fatty acids as analternative for fish oilrdquo Food Chemistry vol 160 pp 393ndash4002014
[116] P Zhao Z Zang X Xie A Huang and G Wang ldquoTheinfluence of different flocculants on the physiological activityand fucoxanthin production of Phaeodactylum tricornutumrdquoProcess Biochemistry vol 49 no 4 pp 681ndash687 2014
[117] D Moreau C Tomasoni C Jacquot et al ldquoCultivated microal-gae and the carotenoid fucoxanthin from Odontella auritaas potent anti-proliferative agents in bronchopulmonary andepithelial cell linesrdquo Environmental Toxicology and Pharmacol-ogy vol 22 no 1 pp 97ndash103 2006
[118] H Maeda M Hosokawa T Sashima K Funayama and KMiyashita ldquoFucoxanthin from edible seaweed Undaria pinnati-fida shows antiobesity effect through UCP1 expression in whiteadipose tissuesrdquo Biochemical and Biophysical Research Commu-nications vol 332 no 2 pp 392ndash397 2005
[119] J E Piero Estrada P Bermejo Bescos and A M Villar delFresno ldquoAntioxidant activity of different fractions of Spirulinaplatensis protean extractrdquo IL Farmaco vol 56 no 5ndash7 pp 497ndash500 2001
[120] S-M Kang S-J Heo K-N Kim S-H Lee and Y-JJeon ldquoIsolation and identification of new compound 2710158401015840-phloroglucinol-661015840-bieckol from brown algae Ecklonia cavaand its antioxidant effectrdquo Journal of Functional Foods vol 4no 1 pp 158ndash166 2012
[121] HHAbdEl-Baky F K El Baz andG S El-Baroty ldquoProductionof phenolic compounds from Spirulinamaximamicroalgae andits protective effectsrdquoAfrican Journal of Biotechnology vol 8 no24 pp 7059ndash7067 2009
[122] A C Guedes H M Amaro and F X Malcata ldquoMicroalgae assources of carotenoidsrdquoMarineDrugs vol 9 no 4 pp 625ndash6442011
[123] G L Renju G M Kurup and K C H Saritha ldquoEffect oflycopene from Chlorella marina on high cholesterol-inducedoxidative damage and inflammation in ratsrdquo Inflammopharma-cology vol 22 no 1 pp 45ndash54 2014
[124] G L Renju G M Kurup and C H S Kumari ldquoAnti-inflammatory activity of lycopene isolated from Chlorellamarina onType II Collagen induced arthritis in SpragueDawleyratsrdquo Immunopharmacology and Immunotoxicology vol 35 no2 pp 282ndash291 2013
[125] C Vılchez E Forjan M Cuaresma F Bedmar I Garbayo andJ M Vega ldquoMarine carotenoids biological functions andcommercial applicationsrdquo Marine Drugs vol 9 no 3 pp 319ndash333 2011
[126] G Richardson ldquoBeyond eye healthrdquo Life Extension Magazine2011 httpwwwleforgMagazine20117Beyond-Eye-HealthPage-01
[127] M Abidov Z Ramazanov R Seifulla and S Grachev ldquoTheeffects of Xanthigen in the weight management of obesepremenopausal women with non-alcoholic fatty liver diseaseand normal liver fatrdquo Diabetes Obesity and Metabolism vol 12no 1 pp 72ndash81 2010
[128] H M Ragap R H Khalil and H HMutawie ldquoImmunostimu-lant effects of dietary Spirulina platensis on tilapia Oreochromisniloticusrdquo Journal of Applied Pharmaceutical Science vol 2 no2 pp 26ndash31 2012
[129] W Xu Z Gao Z Qi M Qiu J-Q Peng and R Shao ldquoEffect ofdietary chlorella on the growth performance and physiologicalparameters of gibel carp Carassius auratus gibeliordquo TurkishJournal of Fisheries and Aquatic Sciences vol 14 no 1 pp 53ndash572014
[130] P Amaninejad H Emadi M Ematiazjoo et al ldquoEffects ofDunaliella microalgae (Dunaliella salina) on different level of
BioMed Research International 15
IgM Immunoglobulin in rainbow trout (Oncrohynchusmykiss)rdquoGlobal Journal of Biodiversity Science and Management vol 3no 2 pp 237ndash242 2013
[131] V Mimouni L Ulmann V Pasquet et al ldquoThe potential ofmicroalgae for the production of bioactive molecules of phar-maceutical interestrdquoCurrent Pharmaceutical Biotechnology vol13 no 15 pp 2733ndash2750 2012
[132] S M Tosh and S Yada ldquoDietary fibres in pulse seeds and frac-tions characterization functional attributes and applicationsrdquoFood Research International vol 43 no 2 pp 450ndash460 2010
[133] H M Amaro R Barros A C Guedes I Sousa-Pinto and FXMalcata ldquoMicroalgal compoundsmodulate carcinogenesis inthe gastrointestinal tractrdquo Trends in Biotechnology vol 31 no 2pp 92ndash98 2013
[134] S S M Mostafa ldquoMicroalgal biotechnology prospects andapplicationsrdquo in Plant Science chapter 12 pp 275ndash314 InTech2012
[135] L Custodio T Justo L Silvestre et al ldquoMicroalgae of dif-ferent phyla display antioxidant metal chelating and acetyl-cholinesterase inhibitory activitiesrdquoFoodChemistry vol 131 no1 pp 134ndash140 2012
[136] C-CHu J-T Lin F-J Lu F-P Chou andD-J Yang ldquoDetermi-nation of carotenoids in Dunaliella salina cultivated in Taiwanand antioxidant capacity of the algal carotenoid extractrdquo FoodChemistry vol 109 no 2 pp 439ndash446 2008
as well as antitumor activity [46] Chlorella is produced bymore than 70 companies Taiwan Chlorella ManufacturingCo (Taipei Taiwan) is the worldrsquos largest producer ofChlorella with over 400000 tons of biomass producedper year (httpwwwtaiwanchlorellacomindexphp) Sig-nificant production also occurs in Klotze (Germany) (80ndash100 t yrminus1 of dry biomass) [47]
24 Dunaliella Dunaliella is a green unicellular halotol-erant microalga that belongs to the Chlorophyceae group(Figure 4) This microalga is widely studied due to its tol-erance of extreme habitat conditions physiological aspectsand its many biotechnological applications Dunaliella is asource of carotenoids glycerol lipids and other bioactivecompounds such as enzymes and vitamins [48 49]
This microalga is a major source of natural 120573-caroteneable to produce up to 14 of its dry weight under conditionsof high salinity light and temperature as well as nutrientlimitation [50] In addition to 120573-carotene this microalgais rich in protein and essential fatty acids which can beconsumed safely as evidenced by GRAS recognition [22]Table 5 presents some compounds that have been extractedfrom microalgae of the Dunaliella genus
Compounds in the Dunaliella biomass have various bio-logical activities such as antioxidant antihypertensive bron-chodilatory analgesic muscle relaxant hepatoprotective andantiedemal properties The microalgal biomass can also be
used directly in food and pharmaceutical formulations [2251]
Chang et al [52] showed that Dunaliella cells containedantibiotic substances According to these authors the crudeextract of this microalga strongly inhibited the growthof Staphylococcus aureus Bacillus cereus Bacillus subtilisand Enterobacter aerogenes In another study Dunaliellamicroalga also showed antibacterial activity against variousmicroorganisms of importance to the food industry includ-ing Escherichia coli Staphylococcus aureus Candida albicansand Aspergillus niger [49 53]
Under ideal growing conditions Dunaliella can be stim-ulated to produce approximately 400mg of 120573-carotene persquare meter of growing area The cultivation of Dunaliellafor the production of 120573-carotene has been conducted inseveral countries including Australia Israel the USA andChina [54ndash56] An ingredient of Dunaliella with a strongability to stimulate cell proliferation and improve the energymetabolism of the skin was released by Pentapharm (BaselSwitzerland) [57] New pilot plants are under development inIndia Chile Mexico Cuba Iran Taiwan Japan Spain andKuwait [50]
3 Cultivation Conditions
The conditions for microalgal cultivation are important fac-tors that influence the metabolism of these microorganismsthus directing the synthesis of specific compounds of interestSeveral researchers have noted the influence of incubationtemperature the pH of themedium the period of cultivationaswell as salinity light intensity andmediumconstituents onthe synthesis of antimicrobial agents [58]
31 pH Temperature and Luminescence pH adjustments arethe primary measures used to prevent contamination bymicroorganisms such as other microalgae species pH con-trol is also essential for effective absorption of the compo-nents of the culture medium because it directly affects theavailability of various chemical elements [59] The reductionof some nutrients in the culturemedium can lead the produc-ing of specific biocompounds The difficulty of consuminga nitrogen source for example can lead microalgae to shiftyourmetabolism for lipids or carbohydrates production [60]
Light is an indispensable factor for photosynthesis caus-ing the cells to reproduce and thereby increasing the cell
6 BioMed Research International
Table 5 Bioactive compounds extracted from the microalgae of the Dunaliella genus
concentration [61] The illuminance also influences the bio-chemical composition of the biomass [62] The fatty acidcontent can be reducedwith increasing light incidenceThis isbecause lipids are the major components of chloroplasts andthe increased light energy demand greater activity of chloro-plasts [63] Studies also show the influence of illuminanceon the microalgae antioxidants According to Madhyastha[64] the application of blue light in the cultivation of themicroalga Spirulina fusiformis through a phenomenon wherethe microalgae cells alter the sequence of amino acids withcysteine repeats enhanced the antioxidant capacity
One of the most important factors for the growth of allliving organisms is the temperature The specific growth rateof the microalgae is directly correlated with the gross rate ofCO2
fixationO2
production (photosynthesis) and the respi-ration rate Photosynthesis and respiration are temperature-dependent with the respiration rate increasing exponentiallywith temperature [65] Temperature has a great influenceon the production of biomass proteins lipids and phenoliccompounds from microalgae The optimum temperature forcultivation of microalgae is 35ndash37∘C [66] In studies con-ducted by Noaman [58] that were performed to verifywhich culture conditions stimulated the greatest produc-tion of antimicrobial agents by the microalga Synechococcusleopoliensis it was observed that a temperature of 35∘C andpH 8 produced a maximum concentration of this bioactivecompound
32 Bioreactors Microalgae have attracted much interest forproduction of bioactive compounds and in order to growand tap the potentials of algae efficient photobioreactors arerequired A good number of photobioreactors can be used inproduction of various algal products [67] Innovative culti-vation systems andmodification of biochemical compositionof microalgae by simple changes in the growth media andcultivation conditions (nutrients light intensity temperaturepH mixing etc) can lead to higher productivity of thetargeted products [68]
Bioreactors can be classified as open or closed Closedphotobioreactors have attracted much interest because theyallow a better control of the cultivation conditions than opensystems One of the major advantages of open ponds is thatthey are easier to construct and operate than most closedsystems [67]
In open systems temperature is a main limiting factoras are variations in solar radiation that lead to low biomassconcentrations However open systems are the most widely
used due to their economic viability Closed systems aregenerally used on a pilot scale for investigating problemsrelated to economic viability Furthermore the use of closedsystems is primarily used for microalgal species that do notgrow in a highly selective medium avoiding contaminationof the cultures [69]
Closed bioreactors can provide high productivity gen-erating greater microalgal biomass per unit time Otheradvantages of the use of closed bioreactors compared withopen systems include the following (i) virtually zero losses inconnection with evaporation (ii) a marked reduction ofproblems related to culture contamination by heterotrophicalgae or othermicroorganisms (iii) ease of biomass collectionprocedures due to smaller volumes of culture medium (iv)greater control of gas exchange between the culture andthe atmosphere (v) a smaller occupied space (vi) a highsurfacevolume ratio which helps to increase the illuminationof the system and (vii) the possibility of obtaining high puritycultures [59]
33 Nutrients The metabolism of microalgae can beautotrophic or heterotrophic The former requires onlyinorganic compounds such as CO
2
salts and solar energythe latter is not photosynthetic requiring an external sourceof organic compounds for use as a nutrient and energy sourceSome photosynthetic species are mixotrophic having theability to perform photosynthesis and use exogenous organicsources simultaneously [70]
Microalgae react to changes in their external environmentwith changes in their intracellular environment Thus themanipulation of the culture conditions or the presence orabsence of nutrients stimulates the biosynthesis of specificcompounds This fact was first referenced by Richmond[71] who changed the composition of Chlorella biomassparticularly in their protein and lipid content by varyingcultivation conditions
Noaman [58] found that leucine combined with citrateor acetate is the sources of nitrogen and carbon that pro-duced higher concentrations of antimicrobial agents in themicroalga Synechococcus leopoliensis Coca et al [72] study-ing the cultivation of Spirulina platensis in a medium sup-plemented with vinasse obtained an increased protein yieldcompared to the unsupplemented culture medium Ip andChen [73] studying the cultivation of Chlorella zofingiensisunder mixotrophic cultivation conditions found that lowconcentrations of nitrate and a high glucose concentrationfavored the production of astaxanthin in this microalga
BioMed Research International 7
Alonso et al [74] studying the influence of nitrogen con-centration in continuous cultivation on lipid concentrationin Phaeodactylum tricornutum noted that there was accu-mulation of saturated and unsaturated fatty acids when thenitrogen source was reduced
Culture media are chemical preparations that are formu-lated to contain the nutrients necessary for the microorgan-isms to multiply andor survive The culture media shouldmeet the nutritional needs of the microorganism assist inprocess control and have a reasonably fixed composition[75]
Among different microalgae variations in the culturemedium are mainly related to the amount of necessary nutri-ents Even so nutritional needs are dependent on environ-mental conditions [59] Microalgae require macronutrientssuch as C N O H P Ca Mg S and K for their growthThe micronutrients that are generally required are Fe MnCu Mo and Co Additionally some species require lowerconcentrations of vitamins in the culture medium [76]
4 Advantages of Using Microalgae to ObtainBioactive Compounds
Microalgae are important sources of bioactive natural sub-stances Many metabolites isolated from these microorgan-isms have shown biological activities and potential healthbenefits [77] Microalgae accumulate specific secondarymetabolites (such as pigments and vitamins) which are highvalue products that have applications in the cosmetic foodor pharmaceutical industries [8 78]
Microalgae live in complex habitats and are subjectedto stress andor extreme conditions such as changes insalinity temperature and nutrients Thus these microorgan-isms must rapidly adapt to new environmental conditions tosurvive and thus produce a great variety of biologically activesecondary metabolites that are not found in other organisms[79] Some of the advantages of microalgal cultivation maybe associated with taxonomic diversity the diverse chemicalcomposition the potential for growth in a bioreactor undercontrolled conditions and the ability to produce activesecondary metabolites in response to the stress induced byextreme exposure conditions [39 80]
In addition to their natural characteristics other impor-tant aspects related to microalgae are the use of solar energyand carbon dioxide (CO
2
) and a high growth rate whichcan produce higher yields compared to higher plants Inaddition microalgae can be grown in areas and climates thatare unsuitable for agriculture therefore microalgae do notcompete with arable food production land The possibility ofcontrolling the production of certain bioactive compoundsby manipulation of culture conditions is another advantageof using microalgae [7 81ndash83]
The cultivation of microalgae is a major mechanism forreducing excess carbon dioxide (CO
2
) in the atmosphere bybiofixation in which an industrial process uses a CO
2
-richgas as a carbon source formicroalgal growthThismechanismcontributes to a reduction of the greenhouse effect and globalwarming further reducing the costs of the carbon source
for growth which is the greatest nutrient requirement formicroalgae [13 84]
The cultivation of microalgae is not seasonal they areimportant for food in aquaculture systems and can effectivelyremove pollutants such as nitrogen and phosphorus fromwastewater Moreover they are themost efficient solar energybiomass converters Microalgae cultivation via sunlight-dependent systems contributes to sustainable developmentand natural resource management [13]
The integration of the production process of bioactivemetabolites in a biorefinery is a sustainable means of energyproduction food production and the production of productswith high added value [7] The biorefinery concept based onmicroalgae depends on the efficient use of biomass throughfractionation resulting in several isolated productsThis con-cept encompasses a biorefinery platform which is capable ofoffering a wide variety of different products such as productswith applications in pharmaceuticals medicine food (pro-tein fiber) and biofuels [7 85] These benefits contribute tothe economic viability of microalgal production [7 8]
5 Bioactive Compounds
Bioactive compounds are physiologically active substanceswith functional properties in the human body There is greatenthusiasm for the development and manufacture of variousbiocompounds that can potentially be used as functionalingredients such as carotenoids phycocyanins polyphenolsfatty acids and polyunsaturated compounds [16]
An interest in the production of bioactive compoundsfrom natural sources has recently emerged driven by agrowing number of scientific studies that demonstrate thebeneficial effects of these compounds on health [80] Naturalproducts are important in the search for new pharmaco-logically active compounds In general they play a role indrug discovery for the treatment of human diseases [86]Many clinically viable and commercially available drugs withantitumor and antiinfective activity originated as naturalproducts
Microalgae are a natural source of interesting biocom-pounds Microalgae are known to produce various therapeu-tically effective biocompounds that can be obtained from thebiomass or released extracellularly into the medium [11]These microorganisms contain many bioactive compoundssuch as proteins polysaccharides lipids vitamins enzymessterols and other high-value compounds with pharmaceu-tical and nutritional importance that can be employed forcommercial use [13]
51 Compounds with Antioxidant Function Oxidative dam-age caused by reactive oxygen species to lipids proteins andnucleic acids can cause many chronic diseases such as heartdisease atherosclerosis cancer and aging Epidemiologicalstudies have demonstrated an inverse association between theintake of fruits and vegetables and mortality from diseasessuch as cancer This phenomenon can be attributed to theantioxidant activity of these foods [87]
8 BioMed Research International
Microalgal biomass is considered a rich natural source ofantioxidants with potential applications in food cosmet-ics and medicine [87] Antioxidant compounds such asdimethylsulfoniopropionate and mycosporine amino acidswere isolated frommicroalgae and are potent chemical block-ers ofUV radiation [88] In addition to these compounds pig-ments lipids and polysaccharides with antioxidant activitycan also be found in microalgal biomass
Carotenoids and phycocyanins are the pigments mostused in scientific research C-phycocyanin (C-PC) is a bluephotosynthetic pigment that belongs to the group of phyco-biliproteins found in large quantities in the cyanobacteriaRhodophyta and Cryptophyte [89] Phycocyanin has appli-cations as a nutrient and natural food colorants and cosmet-ics It is usually extracted from the biomass of Spirulina [90]and Porphyridium cruentum [91] and Synechococcus [89]
Among the carotenoid compounds 120573-carotene andastaxanthin are prominent These compounds have appli-cation in the food and pharmaceutical industries becauseof their antioxidant properties and pigmentation ability Inmicroalgal metabolism they protect photosynthetic tissuesagainst damage caused by light and oxygen [92] Dunaliellasalina is a microalga recognized as a major biological sourceof 120573-carotene pigment producing more than 14 in drybiomass [46] H pluvialis is a source of the pigment astax-anthin producing 1ndash8 of astaxanthin as dry biomass [93]
Polysaccharides represent a class of high value-addedcomponents with applications in food cosmetics fabrics sta-bilizers emulsifiers and medicine [94] Microalgal polysac-charides contain sulphate esters are referred to as sulfatedpolysaccharides and possess unique medical applicationsThe basic mechanism of therapeutic action is based on thestimulation of macrophages and modulation The biologicalactivity of sulfur polysaccharides is linked to their sugarcomposition position and degree of sulfation [95] Amongthe microalgae capable of producing these compounds areChlorella vulgaris Scenedesmus quadricauda [96] and Por-phyridium sp [97]
52 Compounds with Antimicrobial Activity The importanceof discovering new compounds with antimicrobial activityis driven by the development of antibiotic resistance inhumans due to constant clinical use of antibioticsMicroalgaeare an important source of antibiotics with a broad andefficient antibacterial activity [11] The antimicrobial activityof these microorganisms is due to the ability to synthesizecompounds such as fatty acids acrylic acids halogenatedaliphatic compounds terpenoids sterols sulfur-containingheterocyclic compounds carbohydrates acetogenins andphenols [98]
The antimicrobial activity of extracts from microalgae isrelated to its lipid composition The antimicrobial action ofmicroalgae is also noteworthy because of the potential toproduce compounds such as 120572- and 120573-ionone 120573-cyclocitralneophytadiene and phytol [99] Microalgae antimicrobialactivity against human pathogens such as Escherichia coliPseudomonas aeruginosa Staphylococcus aureus and Staphy-lococcus epidermidis has been attributed to 120574-linolenic acid
The mechanism of action of fatty acids affects variousstructures in microorganisms however cell membranes arethe most impacted Membrane damage most likely leadsto a loss of internal substances from the cells and theentry of harmful components reduces nutrient absorption inaddition to inhibiting cellular respiration The ability of fattyacids to interfere with bacterial growth depends on boththeir chain length and the degree of unsaturation Fatty acidswith more than 10 carbon atoms apparently induce lysis ofbacterial protoplasts [99]
Microbial polysaccharides and other biological com-pounds have antiviral and antimicrobial action Microalgaeproduce extracellular sulfated polysaccharide (EPS) withacidic characteristics that has a potential as a therapeuticagent [101] Highly sulfated antiviral polysaccharides fromseveral species of microalgae consist mainly of xylose glu-cose and galactose The EPS sulfate groups determine somecharacteristics of polysaccharides it has been found thathigher sulphate contents induced higher antiviral activities[94 101] The inhibitory effect of polysaccharides of microal-gal origin is due to viral interactions or positive charges onthe cell surface thereby preventing penetration of the virusinto host cells [99]
The cyanobacterium Spirulina (Arthrospira) can producesulfated polysaccharides that have already found applicationsas antiviral agents both in vivo and in vitro [102] Eukaryoticmicroalgae such as Chlorella sp and Dunaliella sp produceand secrete polysaccharides at relatively high levels [17] Theantibacterial ability of Spirulina has been correlated withtheir volatile composition resulting in the identification of15 elements which constitutes 96 of total compounds Themajor volatile components produced by Spirulina consist ofheptadecane (40) and tetradecane (35) [39]
Some studies have reported that sulfated polysaccharidesderived from microalgae inhibit viral infection such asencephalomyocarditis virus Herpes simplex virus types 1and 2 (HSV1 HSV2) human immunodeficiency virus (HIV)hemorrhagic septicemia in salmonid virus swine fever virusand varicella virus [99 103] Carrageenan is a sulfatedpolysaccharide that can directly bind to human papillo-mavirus to inhibit not only the viral adsorption process butalso the input and subsequent process of the uncoating of thevirus [101]
53 Compounds with Anti-Inflammatory Action Inflam-mation is an immediate reaction to a cell or tissueinjury caused by noxious stimuli such as toxins andpathogens In this situation the body recognizes theagents responsible for the attack and attempts to neu-tralize them as quickly as possible Inflammation causesredness swelling heat and pain usually located at thesite of infection [104] Ingestion of anti-inflammatory com-pounds enhances the bodyrsquos immune response and helpsto prevent disease and aids the healing process Microal-gae produce several anti-inflammatory compounds in their
BioMed Research International 9
biomass that may exert a protective function in the bodywhen consumed as food or used as pharmaceuticals andcosmetics
Because of its anti-inflammatory capabilities microalgalbiomass is being considered for applications in tissue engi-neering for the development of scaffolds for use in reconsti-tution of organs and tissues [105 106] This is an importantapplication for humans especially in patients with burnsin which the skin was completely lost [107] Among themost important microalgal compounds with such prop-erties are long-chain polyunsaturated fatty acids (PUFAs)[108 109] sulfurized polysaccharides [110] and pigments[111]
Many microalgal polysaccharides possess the ability tomodulate the immune system through the activation ofmacrophage functions and the induction of reactive oxy-gen species (ROS) nitric oxide (NO) and various othertypes of cytokineschemokines [112] Macrophages are ableto regulate several innate responses and secrete cytokinesand chemocytokines that serve as signals for immune andinflammatory molecular reactions [113] Sulfur polysaccha-rides with anti-inflammatory activity can be applied inskin treatments inhibiting the migration and adhesion ofpolymorphonuclear leukocytes [110] Guzman et al [114]studied the anti-inflammatory capacity of the microalgaChlorella stigmatophora and Phaeodactylum tricomutum andconcluded that bothmicroalgae showed positive responses inthe test of paw edema by carrageenan
The PUFAs especially 1205963 and 1205966 as eicosapentaenoic(EPA) docosahexaenoic (DHA) and arachidonic (AA) acidshave been applied in the treatment of chronic inflammationsuch as rheumatism and skin diseases [108] Ryckebosch etal [115] evaluated the nutritional value of the total lipidsextracted from different PUFAs produced by microalgae Inthis study the microalgae IsochrysisNannochloropsis Phaeo-dactylum Pavlova and Thalassiosira produced 1205963 PUFA asan alternative to fish oil in food
Among the pigments with anti-inflammatory activityfucoxanthin carotenoid found in diatoms [116 117] is capableof stimulating apoptosis in human cancer cells [118] A phy-cocyanin found in cyanobacteria has an anti-inflammatoryactivity that occurs through the inhibition of histaminerelease [111 119]
54 Compounds with Potentiality over Degenerative Dis-eases In humans the oxidation reactions driven by reactiveoxygen species (ROS) can lead to irreversible damage tocellular components including lipids proteins and DNAdegradation andor mutation Consequently this damagecan lead to several syndromes such as cardiovascular dis-ease some cancers and the degenerative diseases of aging[120]
Chronic age-related diseases involve oxidative stress andinflammation and their consequences Chronic inflammationplays a significant role in the mediation of neurodegenerativediseases such as Parkinsonrsquos disease Alzheimerrsquos diseasemultiple sclerosis acquired immunodeficiency syndrome(AIDS) and dementia complex [77]
Natural pigments derived from microalgae (NPs) haveneuroprotective properties being valuable sources as func-tional ingredients in foods and pharmaceutical products thatshow efficient action in the treatment andor prevention ofneurodegenerative diseases Vitamin E has preventive effectsfor many diseases such as atherosclerosis and heart diseaseas well as neurodegenerative diseases such as multiplesclerosis [77]
Carotenoids have great potential benefits to humanhealth including the treatment of degenerative diseases suchas macular degeneration and cataract development Thesecompounds act as antioxidants reducing oxidative damageby ROS Studies indicated that increased intake of phenolsdecreased the occurrence of degenerative diseases Phenoliccompounds from microalgae with the potential to fight freeradicals have been reported [121]
Dunaliella salina is a natural source of 120573-carotene whichproduced a reduced risk of cancer and degenerative diseasesin humans Lutein is effective against various diseases includ-ing cataracts and macular degeneration and in the earlystages of atherosclerosis Extracts of Chlorella sp containing120573-carotene and lutein significantly prevented the cognitivedisability that accompanies Alzheimerrsquos disease in rats It wasalso reported that lutein extracted from Chlorella reducedthe incidence of cancer Likewise carotenoids extractedfrom Chlorella ellipsoidea and Chlorella vulgaris inhibited thegrowth of colon cancer [122] A lycopene extracted fromthe microalgae Chlorella marina significantly reduced theproliferation of prostate cancer inmice [123]This compoundalso reduced total cholesterol and low-density lipoprotein(LDL) levels [123] and improved rheumatoid arthritis [124]
Low plasma levels of lutein have also been associatedwith an increased tendency ofmyocardial infarction whereashigh intake of lutein was related to a decreased risk ofstroke In addition high levels of carotenoids with provi-tamin A activity including 120572-carotene 120573-carotene and 120573-cryptoxanthin have been associated with reduction in therisk of angina pectoris Macular degeneration the lead-ing cause of irreversible vision loss has also been associ-ated with very low consumption of lutein and zeaxanthin[125]
Scientific findings indicate astaxanthin for multimodalintervention formany forms of degenerative diseases includ-ing cardiovascular diseases cancer metabolic syndromecognitive impairment age-related immune dysfunctionstomach and ocular diseases (macular degeneration cataractglaucoma diabetic retinopathy and retinitis pigmentosa)and skin damage [126] High levels of lycopene in plasmaand tissues were inversely related to coronary heart diseasemyocardial infarction and the risk of atherosclerosis [125]
55 Compounds withHealth Promoting Function The impor-tance of microalgae as sources of functional ingredients hasbeen recognized because of their beneficial health effectsNatural pigments are valuable sources of bioactive com-pounds These pigments have various beneficial biologicalactivities such as antioxidant anticancer anti-inflammatoryantiobesity antiangiogenic and neuroprotective action and
10 BioMed Research International
are indicated for the treatment or prevention of severalchronic diseases [77]
The antioxidant potential of carotenoid pigments andtheir ability to prevent cancer aging atherosclerosis coro-nary heart disease and degenerative diseases have beendescribed 120573-Carotene has higher provitamin A activitywhich is essential for vision and the correct functioning ofthe immune system Astaxanthin is linked to many healthbenefits such as protection against lipid peroxidation age-related macular degeneration reduced atherosclerosis andan increased immune response [102]
Fucoxanthin is considered as a promising dietary andweight loss supplement and for the treatment of obesityClinical studies by Abidov et al [127] demonstrated the effectof ldquoxanthigenrdquo a fucoxanthin based antiobesity supplementFurthermore fucoxanthinmay be useful for the prevention ofbone diseases such as osteoporosis and rheumatoid arthritisIt has also been reported to be effective for the therapeutictreatment of diabetic diseases suppressing insulin and hyper-glycemia [77]
Microalgae proteins are of great interest as a source ofbioactive peptides due to their therapeutic potential in thetreatment of various diseases [7] Proteins peptides andamino acids have functions that contribute to health benefitsThese compounds can include growth factors hormones andimmunomodulators and can help to replace damaged tissuesin addition to providing nutritional benefits Microalgaesuch as Chlorella and Spirulina (Arthrospira) may be usedas nutraceuticals or included in functional foods to preventdiseases and damage to cells and tissues due to their richprotein content and amino acid profile [102]
The antimicrobial action of certain enzymes (eglysozyme) and immunoglobulins has been reported andrecommended for people with different diseases (egCrohnrsquos disease) due to the existence of formulations withpeptides and free amino acids Studies of the healtheffects of lysozyme have been reported in the microalgaeSpirulina platensis [128] Chlorella [129] and Dunaliellasalina [130] Spirulina (Arthrospira) and Chlorella biomasspills are marketed as is ldquoHawaiian Spirulina Pacificardquo(httpspirulinagreennutritionalscomau) Other proteinscan also increase the production of cholecystokinin involvedin appetite suppression and the reduction of LDL-cholesterolProtein peptides from Chlorella have a potential as dietarysupplements for the prevention of oxidative stress-relateddiseases such as atherosclerosis coronary heart disease andcancer [39]
The essential fatty acids 120596-3 and 120596-6 in particular areimportant for the integrity of tissues 120574-Linolenic acid hastherapeutic applications in cosmetics to revitalize the skinand thus slow aging Linoleic and linolenic acids are essentialnutrients for the immune system and other related tissueregeneration processes Linoleic acid is also used for thetreatment of hyperplasia of the skin [102]
The most studied microalgal lipid compounds are thepolyunsaturated fatty acids (PUFAs) docosahexaenoic acid(120596-3 C226) (DHA) eicosapentaenoic acid (C20 120596-35)(EPA) and arachidonic acid (120596-6 C204) (ARA) Studies haveshown that dietary120596-3 PUFAs have a protective effect against
atherosclerotic heart disease [131] DHA and EPA showed theability to reduce problems associated with strokes and arthri-tis besides reducing hypertension lipid content (a decreasein triglycerides and an increase of HDL) and acting asanti-inflammatory agents DHA is also important in thedevelopment and function of the nervous system Further-more ARA and EPA are platelet aggregators vasoconstric-tors and vasodilators and have antiaggregative action on theendothelium as well as chemostatic activity in neutrophils[102]
Other lipid compounds with interesting bioactive prop-erties are the microalgal sterols Phytosterols have demon-strated reduction of total cholesterol (LDL) in humans byinhibiting its absorption from the intestine [50] Polysac-charides can be considered as dietary fibers associatedwith different physiological effects Insoluble fiber (cellulosehemicellulose and lignin) mainly promotes the movementof material through the digestive system thereby improvinglaxation and increasing satietyThey can also be considered asprebiotics because they promote the growth of gutmicrofloraincluding probiotic species Soluble fiber (oligosaccharidespectins and 120573-glucans) may reduce cholesterol and regulateblood glucose [7 132]
6 Conclusion
The proven ability of microalgae to produce bioactive com-pounds places these microorganisms in the biotechnologicalspotlight for applications in various areas of study especiallyin the life sciencesThe production ofmicroalgal metaboliteswhich stimulate defense mechanisms in the human bodyhas spurred intense study of the application of microalgalbiomass in various foods and pharmacological and medicalproducts There is obviously a need for further study of theidentified compounds and their activities in the treatmentand prevention of various diseases in addition to an ongoingsearch for other as yet undetected metabolites
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgment
The authors thank the National Counsel of Technologicaland Scientific Development (CNPq) for the Productivityin Technological Development and Innovative ExtensionScholarship
References
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[2] A A El Gamal ldquoBiological importance of marine algaerdquo SaudiPharmaceutical Journal vol 18 no 1 pp 1ndash25 2010
BioMed Research International 11
[3] I Moreno-Garrido ldquoMicroalgae immobilization current tech-niques and usesrdquo Bioresource Technology vol 99 no 10 pp3949ndash3964 2008
[4] R-B Volk and F H Furkert ldquoAntialgal antibacterial andantifungal activity of two metabolites produced and excretedby cyanobacteria during growthrdquoMicrobiological Research vol161 no 2 pp 180ndash186 2006
[5] R-B Volk ldquoA newly developed assay for the quantitativedetermination of antimicrobial (anticyanobacterial) activity ofboth hydrophilic and lipophilic test compounds without anyrestrictionrdquoMicrobiological Research vol 163 no 2 pp 161ndash1672008
[6] D F Smee K W Bailey M-H Wong et al ldquoTreatment ofinfluenza A (H1N1) virus infections in mice and ferrets withcyanovirin-Nrdquo Antiviral Research vol 80 no 3 pp 266ndash2712008
[7] E Ibanez and A Cifuentes ldquoBenefits of using algae as naturalsources of functional ingredientsrdquo Journal of the Science of Foodand Agriculture vol 93 no 4 pp 703ndash709 2013
[8] G Markou and E Nerantzis ldquoMicroalgae for high-valuecompounds and biofuels production a review with focus oncultivation under stress conditionsrdquo Biotechnology Advancesvol 31 no 8 pp 1532ndash1542 2013
[9] R Harun M Singh G M Forde andM K Danquah ldquoBiopro-cess engineering ofmicroalgae to produce a variety of consumerproductsrdquo Renewable and Sustainable Energy Reviews vol 14no 3 pp 1037ndash1047 2010
[10] C Kolympiris N Kalaitzandonakes and D Miller ldquoPublicfunds and local biotechnology firm creationrdquo Research Policyvol 43 no 1 pp 121ndash137 2014
[11] S Bhagavathy P Sumathi and I Jancy Sherene Bell ldquoGreenalgae Chlorococcum humicola-a new source of bioactive com-pounds with antimicrobial activityrdquo Asian Pacific Journal ofTropical Biomedicine vol 1 no 1 pp S1ndashS7 2011
[12] A M F Palavra J P Coelho J G Barroso et al ldquoSupercrit-ical carbon dioxide extraction of bioactive compounds frommicroalgae and volatile oils from aromatic plantsrdquo Journal ofSupercritical Fluids vol 60 pp 21ndash27 2011
[13] I Priyadarshani and B Rath ldquoCommercial and industrialapplications of micro algaemdasha reviewrdquo Journal of Algal BiomassUtilization vol 3 no 4 pp 89ndash100 2012
[14] JW Blunt B R CoppM H GMunro P T Northcote andMR Prinsep ldquoMarine natural productsrdquoNatural Product Reportsvol 23 no 1 pp 26ndash78 2006
[15] A M S Mayer and M T Hamann ldquoMarine pharmacologyin 2001-2002 marine compounds with anthelmintic antibacte-rial anticoagulant antidiabetic antifungal anti-inflammatoryantimalarial antiplatelet antiprotozoal antituberculosis andantiviral activities affecting the cardiovascular immune andnervous systems and other miscellaneous mechanisms ofactionrdquo Comparative Biochemistry and Physiology Part C Toxi-cology amp Pharmacology vol 140 no 3-4 pp 265ndash286 2005
[16] M Plaza S Santoyo L Jaime et al ldquoScreening for bioactivecompounds from algaerdquo Journal of Pharmaceutical and Biomed-ical Analysis vol 51 no 2 pp 450ndash455 2010
[17] I Rodrıguez-Meizoso L Jaime S Santoyo et al ldquoPressurizedfluid extraction of bioactive compounds from Phormidiumspeciesrdquo Journal of Agricultural and Food Chemistry vol 56 no10 pp 3517ndash3523 2008
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vivo and in vitro aspectsrdquo Brazilian Journal of Pharmacognosyvol 23 no 3 pp 471ndash480 2013
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extraction of 120574-linolenic acid and other lipids from Arthrospira(Spirulina)maxima comparison with organic solvent extrac-tionrdquo Food Chemistry vol 99 no 1 pp 57ndash63 2006
[21] I Romano M R Bellitti B Nicolaus et al ldquoLipid profilea useful chemotaxonomic marker for classification of a newcyanobacterium in Spirulina genusrdquo Phytochemistry vol 54 no3 pp 289ndash294 2000
[22] J A C Costa and M G Morais ldquoMicroalgae for food produc-tionrdquo in Fermentation Process Engineering in the Food IndustryC R Soccol A Pandey and C Larroche Eds p 486 Taylor ampFrancis 2013
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[79] I Rodrıguez-Meizoso L Jaime S Santoyo F J Senorans ACifuentes and E Ibanez ldquoSubcritical water extraction andcharacterization of bioactive compounds from Haematococcuspluvialis microalgardquo Journal of Pharmaceutical and BiomedicalAnalysis vol 51 no 2 pp 456ndash463 2010
[80] M Herrero M Castro-Puyana J A Mendiola and E IbanezldquoCompressed fluids for the extraction of bioactive compoundsrdquoTrends in Analytical Chemistry vol 43 pp 67ndash83 2013
[81] N K Singh and D W Dhar ldquoMicroalgae as second generationbiofuel A reviewrdquo Agronomy for Sustainable Development vol31 no 4 pp 605ndash629 2011
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production of bioactive compounds from Tetraselmis suecica atpilot scalerdquo Journal of Cleaner Production vol 64 pp 323ndash3312014
[85] B Subhadra ldquoAlgal biorefinery-based industry an approachto address fuel and food insecurity for a carbon-smart worldrdquoJournal of the Science of Food and Agriculture vol 91 no 1 pp2ndash13 2011
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[94] S Arad and O Levy-Ontman ldquoRed microalgal cell-wallpolysaccharides biotechnological aspectsrdquo Current Opinion inBiotechnology vol 21 no 3 pp 358ndash364 2010
[95] M Kim J H Yim S-Y Kim et al ldquoIn vitro inhibitionof influenza A virus infection by marine microalga-derivedsulfated polysaccharide p-KG03rdquoAntiviral Research vol 93 no2 pp 253ndash259 2012
[96] Z A Mohamed ldquoPolysaccharides as a protective responseagainst microcystin-induced oxidative stress in Chlorella vul-garis and Scenedesmus quadricauda and their possible signifi-cance in the aquatic ecosystemrdquo Ecotoxicology vol 17 no 6 pp504ndash516 2008
[97] T Tannin-Spitz M Bergman D Van-Moppes S Grossmanand S Arad ldquoAntioxidant activity of the polysaccharide of thered microalga Porphyridium sprdquo Journal of Applied Phycologyvol 17 no 3 pp 215ndash222 2005
[98] J W Prakash M Johnson and S Jeeva ldquoAntimicrobial activityof certain fresh water microalgae from Thamirabarani RiverTamil Nadu South Indiardquo Asian Pacific Journal of TropicalBiomedicine vol 1 supplement no 2 pp S170ndashS173 2011
[99] H M Amaro A C Guedes and F X Malcata ldquoAntimicrobialactivities of microalgae an invited reviewrdquo in Science againstMicrobial Pathogens Communicating Current Research andTechnological Advances A Mendez-Vilas Ed pp 1272ndash12802011
[100] V J Smith A PDesbois and E ADyrynda ldquoConventional andunconventional antimicrobials from fish marine invertebratesand micro-algaerdquo Marine Drugs vol 8 no 4 pp 1213ndash12622010
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[101] M F D J Raposo A M M B de Morais and R M SC de Morais ldquoInfluence of sulphate on the composition andantibacterial and antiviral properties of the exopolysaccharidefrom Porphyridium cruentumrdquo Life Sciences vol 101 no 1-2 pp56ndash63 2014
[102] M F De Jesus Raposo R M S C De Morais and A M M BDe Morais ldquoHealth applications of bioactive compounds frommarine microalgaerdquo Life Sciences vol 93 no 15 pp 479ndash4862013
[103] A Smelcerovic Z Knezevic-Jugovic and Z PetronijevicldquoMicrobial polysaccharides and their derivatives as current andprospective pharmaceuticalsrdquo Current Pharmaceutical Designvol 14 no 29 pp 3168ndash3195 2008
[104] M T Madigan J M Martinko P V Dunlap and D P ClarkMicrobiologia de Brock Artmed Editora 12th edition 2010
[105] M G de Morais J A V Costa P H L Pranke et alldquoDevelopment of a newnanofiber scaffold for usewith stemcellsin a third degree burn animal modelrdquo Burns Oxford vol 40 no8 pp 1650ndash1660 2014
[106] M G de Morais C Stillings R Dersch et al ldquoPreparation ofnanofibers containing the microalga Spirulina (Arthrospira)rdquoBioresource Technology vol 101 no 8 pp 2872ndash2876 2010
[107] D Steffens M Lersch A Rosa et al ldquoA new biomaterialof nanofibers with the microalga Spirulina as scaffolds tocultivate with stem cells for use in tissue engineeringrdquo Journalof Biomedical Nanotechnology vol 9 no 4 pp 710ndash718 2013
[108] C Barrow and F ShahidiMarine Nutraceuticals and FunctionalFoods CRC Press Taylor amp Francis Boca Raton Fla USA2008
[109] M N A Khan J-Y ChoM-C Lee et al ldquoIsolation of two anti-inflammatory and one pro-inflammatory polyunsaturated fattyacids from the brown seaweed Undaria pinnatifidardquo Journal ofAgricultural and Food Chemistry vol 55 no 17 pp 6984ndash69882007
[110] M S Matsui N Muizzuddin S Arad and K MarenusldquoSulfated polysaccharides from redmicroalgae have antiinflam-matory properties in vitro and in vivordquo Applied Biochemistryand Biotechnology vol 104 no 1 pp 13ndash22 2003
[111] V B Bhat and K M Madyastha ldquoScavenging of peroxynitriteby phycocyanin and phycocyanobilin from Spirulina platensisprotection against oxidative damage to DNArdquo Biochemical andBiophysical Research Communications vol 285 no 2 pp 262ndash266 2001
[112] I A Schepetkin and M T Quinn ldquoBotanical polysaccharidesmacrophage immunomodulation and therapeutic potentialrdquoInternational Immunopharmacology vol 6 no 3 pp 317ndash3332006
[113] J K Park Z-H Kim C G Lee et al ldquoCharacterization andimmunostimulating activity of a water-soluble polysaccharideisolated from Haematococcus lacustrisrdquo Biotechnology and Bio-process Engineering vol 16 no 6 pp 1090ndash1098 2011
[114] S Guzman A Gato M Lamela M Freire-Garabal and J MCalleja ldquoAnti-inflammatory and immunomodulatory activitiesof polysaccharide from Chlorella stigmatophora and Phaeo-dactylum tricornutumrdquo Phytotherapy Research vol 17 no 6 pp665ndash670 2003
[115] E Ryckebosch C Bruneel R Termote-Verhalle K Goiris KMuylaert and I Foubert ldquoNutritional evaluation of microalgaeoils rich in omega-3 long chain polyunsaturated fatty acids as analternative for fish oilrdquo Food Chemistry vol 160 pp 393ndash4002014
[116] P Zhao Z Zang X Xie A Huang and G Wang ldquoTheinfluence of different flocculants on the physiological activityand fucoxanthin production of Phaeodactylum tricornutumrdquoProcess Biochemistry vol 49 no 4 pp 681ndash687 2014
[117] D Moreau C Tomasoni C Jacquot et al ldquoCultivated microal-gae and the carotenoid fucoxanthin from Odontella auritaas potent anti-proliferative agents in bronchopulmonary andepithelial cell linesrdquo Environmental Toxicology and Pharmacol-ogy vol 22 no 1 pp 97ndash103 2006
[118] H Maeda M Hosokawa T Sashima K Funayama and KMiyashita ldquoFucoxanthin from edible seaweed Undaria pinnati-fida shows antiobesity effect through UCP1 expression in whiteadipose tissuesrdquo Biochemical and Biophysical Research Commu-nications vol 332 no 2 pp 392ndash397 2005
[119] J E Piero Estrada P Bermejo Bescos and A M Villar delFresno ldquoAntioxidant activity of different fractions of Spirulinaplatensis protean extractrdquo IL Farmaco vol 56 no 5ndash7 pp 497ndash500 2001
[120] S-M Kang S-J Heo K-N Kim S-H Lee and Y-JJeon ldquoIsolation and identification of new compound 2710158401015840-phloroglucinol-661015840-bieckol from brown algae Ecklonia cavaand its antioxidant effectrdquo Journal of Functional Foods vol 4no 1 pp 158ndash166 2012
[121] HHAbdEl-Baky F K El Baz andG S El-Baroty ldquoProductionof phenolic compounds from Spirulinamaximamicroalgae andits protective effectsrdquoAfrican Journal of Biotechnology vol 8 no24 pp 7059ndash7067 2009
[122] A C Guedes H M Amaro and F X Malcata ldquoMicroalgae assources of carotenoidsrdquoMarineDrugs vol 9 no 4 pp 625ndash6442011
[123] G L Renju G M Kurup and K C H Saritha ldquoEffect oflycopene from Chlorella marina on high cholesterol-inducedoxidative damage and inflammation in ratsrdquo Inflammopharma-cology vol 22 no 1 pp 45ndash54 2014
[124] G L Renju G M Kurup and C H S Kumari ldquoAnti-inflammatory activity of lycopene isolated from Chlorellamarina onType II Collagen induced arthritis in SpragueDawleyratsrdquo Immunopharmacology and Immunotoxicology vol 35 no2 pp 282ndash291 2013
[125] C Vılchez E Forjan M Cuaresma F Bedmar I Garbayo andJ M Vega ldquoMarine carotenoids biological functions andcommercial applicationsrdquo Marine Drugs vol 9 no 3 pp 319ndash333 2011
[126] G Richardson ldquoBeyond eye healthrdquo Life Extension Magazine2011 httpwwwleforgMagazine20117Beyond-Eye-HealthPage-01
[127] M Abidov Z Ramazanov R Seifulla and S Grachev ldquoTheeffects of Xanthigen in the weight management of obesepremenopausal women with non-alcoholic fatty liver diseaseand normal liver fatrdquo Diabetes Obesity and Metabolism vol 12no 1 pp 72ndash81 2010
[128] H M Ragap R H Khalil and H HMutawie ldquoImmunostimu-lant effects of dietary Spirulina platensis on tilapia Oreochromisniloticusrdquo Journal of Applied Pharmaceutical Science vol 2 no2 pp 26ndash31 2012
[129] W Xu Z Gao Z Qi M Qiu J-Q Peng and R Shao ldquoEffect ofdietary chlorella on the growth performance and physiologicalparameters of gibel carp Carassius auratus gibeliordquo TurkishJournal of Fisheries and Aquatic Sciences vol 14 no 1 pp 53ndash572014
[130] P Amaninejad H Emadi M Ematiazjoo et al ldquoEffects ofDunaliella microalgae (Dunaliella salina) on different level of
BioMed Research International 15
IgM Immunoglobulin in rainbow trout (Oncrohynchusmykiss)rdquoGlobal Journal of Biodiversity Science and Management vol 3no 2 pp 237ndash242 2013
[131] V Mimouni L Ulmann V Pasquet et al ldquoThe potential ofmicroalgae for the production of bioactive molecules of phar-maceutical interestrdquoCurrent Pharmaceutical Biotechnology vol13 no 15 pp 2733ndash2750 2012
[132] S M Tosh and S Yada ldquoDietary fibres in pulse seeds and frac-tions characterization functional attributes and applicationsrdquoFood Research International vol 43 no 2 pp 450ndash460 2010
[133] H M Amaro R Barros A C Guedes I Sousa-Pinto and FXMalcata ldquoMicroalgal compoundsmodulate carcinogenesis inthe gastrointestinal tractrdquo Trends in Biotechnology vol 31 no 2pp 92ndash98 2013
[134] S S M Mostafa ldquoMicroalgal biotechnology prospects andapplicationsrdquo in Plant Science chapter 12 pp 275ndash314 InTech2012
[135] L Custodio T Justo L Silvestre et al ldquoMicroalgae of dif-ferent phyla display antioxidant metal chelating and acetyl-cholinesterase inhibitory activitiesrdquoFoodChemistry vol 131 no1 pp 134ndash140 2012
[136] C-CHu J-T Lin F-J Lu F-P Chou andD-J Yang ldquoDetermi-nation of carotenoids in Dunaliella salina cultivated in Taiwanand antioxidant capacity of the algal carotenoid extractrdquo FoodChemistry vol 109 no 2 pp 439ndash446 2008
concentration [61] The illuminance also influences the bio-chemical composition of the biomass [62] The fatty acidcontent can be reducedwith increasing light incidenceThis isbecause lipids are the major components of chloroplasts andthe increased light energy demand greater activity of chloro-plasts [63] Studies also show the influence of illuminanceon the microalgae antioxidants According to Madhyastha[64] the application of blue light in the cultivation of themicroalga Spirulina fusiformis through a phenomenon wherethe microalgae cells alter the sequence of amino acids withcysteine repeats enhanced the antioxidant capacity
One of the most important factors for the growth of allliving organisms is the temperature The specific growth rateof the microalgae is directly correlated with the gross rate ofCO2
fixationO2
production (photosynthesis) and the respi-ration rate Photosynthesis and respiration are temperature-dependent with the respiration rate increasing exponentiallywith temperature [65] Temperature has a great influenceon the production of biomass proteins lipids and phenoliccompounds from microalgae The optimum temperature forcultivation of microalgae is 35ndash37∘C [66] In studies con-ducted by Noaman [58] that were performed to verifywhich culture conditions stimulated the greatest produc-tion of antimicrobial agents by the microalga Synechococcusleopoliensis it was observed that a temperature of 35∘C andpH 8 produced a maximum concentration of this bioactivecompound
32 Bioreactors Microalgae have attracted much interest forproduction of bioactive compounds and in order to growand tap the potentials of algae efficient photobioreactors arerequired A good number of photobioreactors can be used inproduction of various algal products [67] Innovative culti-vation systems andmodification of biochemical compositionof microalgae by simple changes in the growth media andcultivation conditions (nutrients light intensity temperaturepH mixing etc) can lead to higher productivity of thetargeted products [68]
Bioreactors can be classified as open or closed Closedphotobioreactors have attracted much interest because theyallow a better control of the cultivation conditions than opensystems One of the major advantages of open ponds is thatthey are easier to construct and operate than most closedsystems [67]
In open systems temperature is a main limiting factoras are variations in solar radiation that lead to low biomassconcentrations However open systems are the most widely
used due to their economic viability Closed systems aregenerally used on a pilot scale for investigating problemsrelated to economic viability Furthermore the use of closedsystems is primarily used for microalgal species that do notgrow in a highly selective medium avoiding contaminationof the cultures [69]
Closed bioreactors can provide high productivity gen-erating greater microalgal biomass per unit time Otheradvantages of the use of closed bioreactors compared withopen systems include the following (i) virtually zero losses inconnection with evaporation (ii) a marked reduction ofproblems related to culture contamination by heterotrophicalgae or othermicroorganisms (iii) ease of biomass collectionprocedures due to smaller volumes of culture medium (iv)greater control of gas exchange between the culture andthe atmosphere (v) a smaller occupied space (vi) a highsurfacevolume ratio which helps to increase the illuminationof the system and (vii) the possibility of obtaining high puritycultures [59]
33 Nutrients The metabolism of microalgae can beautotrophic or heterotrophic The former requires onlyinorganic compounds such as CO
2
salts and solar energythe latter is not photosynthetic requiring an external sourceof organic compounds for use as a nutrient and energy sourceSome photosynthetic species are mixotrophic having theability to perform photosynthesis and use exogenous organicsources simultaneously [70]
Microalgae react to changes in their external environmentwith changes in their intracellular environment Thus themanipulation of the culture conditions or the presence orabsence of nutrients stimulates the biosynthesis of specificcompounds This fact was first referenced by Richmond[71] who changed the composition of Chlorella biomassparticularly in their protein and lipid content by varyingcultivation conditions
Noaman [58] found that leucine combined with citrateor acetate is the sources of nitrogen and carbon that pro-duced higher concentrations of antimicrobial agents in themicroalga Synechococcus leopoliensis Coca et al [72] study-ing the cultivation of Spirulina platensis in a medium sup-plemented with vinasse obtained an increased protein yieldcompared to the unsupplemented culture medium Ip andChen [73] studying the cultivation of Chlorella zofingiensisunder mixotrophic cultivation conditions found that lowconcentrations of nitrate and a high glucose concentrationfavored the production of astaxanthin in this microalga
BioMed Research International 7
Alonso et al [74] studying the influence of nitrogen con-centration in continuous cultivation on lipid concentrationin Phaeodactylum tricornutum noted that there was accu-mulation of saturated and unsaturated fatty acids when thenitrogen source was reduced
Culture media are chemical preparations that are formu-lated to contain the nutrients necessary for the microorgan-isms to multiply andor survive The culture media shouldmeet the nutritional needs of the microorganism assist inprocess control and have a reasonably fixed composition[75]
Among different microalgae variations in the culturemedium are mainly related to the amount of necessary nutri-ents Even so nutritional needs are dependent on environ-mental conditions [59] Microalgae require macronutrientssuch as C N O H P Ca Mg S and K for their growthThe micronutrients that are generally required are Fe MnCu Mo and Co Additionally some species require lowerconcentrations of vitamins in the culture medium [76]
4 Advantages of Using Microalgae to ObtainBioactive Compounds
Microalgae are important sources of bioactive natural sub-stances Many metabolites isolated from these microorgan-isms have shown biological activities and potential healthbenefits [77] Microalgae accumulate specific secondarymetabolites (such as pigments and vitamins) which are highvalue products that have applications in the cosmetic foodor pharmaceutical industries [8 78]
Microalgae live in complex habitats and are subjectedto stress andor extreme conditions such as changes insalinity temperature and nutrients Thus these microorgan-isms must rapidly adapt to new environmental conditions tosurvive and thus produce a great variety of biologically activesecondary metabolites that are not found in other organisms[79] Some of the advantages of microalgal cultivation maybe associated with taxonomic diversity the diverse chemicalcomposition the potential for growth in a bioreactor undercontrolled conditions and the ability to produce activesecondary metabolites in response to the stress induced byextreme exposure conditions [39 80]
In addition to their natural characteristics other impor-tant aspects related to microalgae are the use of solar energyand carbon dioxide (CO
2
) and a high growth rate whichcan produce higher yields compared to higher plants Inaddition microalgae can be grown in areas and climates thatare unsuitable for agriculture therefore microalgae do notcompete with arable food production land The possibility ofcontrolling the production of certain bioactive compoundsby manipulation of culture conditions is another advantageof using microalgae [7 81ndash83]
The cultivation of microalgae is a major mechanism forreducing excess carbon dioxide (CO
2
) in the atmosphere bybiofixation in which an industrial process uses a CO
2
-richgas as a carbon source formicroalgal growthThismechanismcontributes to a reduction of the greenhouse effect and globalwarming further reducing the costs of the carbon source
for growth which is the greatest nutrient requirement formicroalgae [13 84]
The cultivation of microalgae is not seasonal they areimportant for food in aquaculture systems and can effectivelyremove pollutants such as nitrogen and phosphorus fromwastewater Moreover they are themost efficient solar energybiomass converters Microalgae cultivation via sunlight-dependent systems contributes to sustainable developmentand natural resource management [13]
The integration of the production process of bioactivemetabolites in a biorefinery is a sustainable means of energyproduction food production and the production of productswith high added value [7] The biorefinery concept based onmicroalgae depends on the efficient use of biomass throughfractionation resulting in several isolated productsThis con-cept encompasses a biorefinery platform which is capable ofoffering a wide variety of different products such as productswith applications in pharmaceuticals medicine food (pro-tein fiber) and biofuels [7 85] These benefits contribute tothe economic viability of microalgal production [7 8]
5 Bioactive Compounds
Bioactive compounds are physiologically active substanceswith functional properties in the human body There is greatenthusiasm for the development and manufacture of variousbiocompounds that can potentially be used as functionalingredients such as carotenoids phycocyanins polyphenolsfatty acids and polyunsaturated compounds [16]
An interest in the production of bioactive compoundsfrom natural sources has recently emerged driven by agrowing number of scientific studies that demonstrate thebeneficial effects of these compounds on health [80] Naturalproducts are important in the search for new pharmaco-logically active compounds In general they play a role indrug discovery for the treatment of human diseases [86]Many clinically viable and commercially available drugs withantitumor and antiinfective activity originated as naturalproducts
Microalgae are a natural source of interesting biocom-pounds Microalgae are known to produce various therapeu-tically effective biocompounds that can be obtained from thebiomass or released extracellularly into the medium [11]These microorganisms contain many bioactive compoundssuch as proteins polysaccharides lipids vitamins enzymessterols and other high-value compounds with pharmaceu-tical and nutritional importance that can be employed forcommercial use [13]
51 Compounds with Antioxidant Function Oxidative dam-age caused by reactive oxygen species to lipids proteins andnucleic acids can cause many chronic diseases such as heartdisease atherosclerosis cancer and aging Epidemiologicalstudies have demonstrated an inverse association between theintake of fruits and vegetables and mortality from diseasessuch as cancer This phenomenon can be attributed to theantioxidant activity of these foods [87]
8 BioMed Research International
Microalgal biomass is considered a rich natural source ofantioxidants with potential applications in food cosmet-ics and medicine [87] Antioxidant compounds such asdimethylsulfoniopropionate and mycosporine amino acidswere isolated frommicroalgae and are potent chemical block-ers ofUV radiation [88] In addition to these compounds pig-ments lipids and polysaccharides with antioxidant activitycan also be found in microalgal biomass
Carotenoids and phycocyanins are the pigments mostused in scientific research C-phycocyanin (C-PC) is a bluephotosynthetic pigment that belongs to the group of phyco-biliproteins found in large quantities in the cyanobacteriaRhodophyta and Cryptophyte [89] Phycocyanin has appli-cations as a nutrient and natural food colorants and cosmet-ics It is usually extracted from the biomass of Spirulina [90]and Porphyridium cruentum [91] and Synechococcus [89]
Among the carotenoid compounds 120573-carotene andastaxanthin are prominent These compounds have appli-cation in the food and pharmaceutical industries becauseof their antioxidant properties and pigmentation ability Inmicroalgal metabolism they protect photosynthetic tissuesagainst damage caused by light and oxygen [92] Dunaliellasalina is a microalga recognized as a major biological sourceof 120573-carotene pigment producing more than 14 in drybiomass [46] H pluvialis is a source of the pigment astax-anthin producing 1ndash8 of astaxanthin as dry biomass [93]
Polysaccharides represent a class of high value-addedcomponents with applications in food cosmetics fabrics sta-bilizers emulsifiers and medicine [94] Microalgal polysac-charides contain sulphate esters are referred to as sulfatedpolysaccharides and possess unique medical applicationsThe basic mechanism of therapeutic action is based on thestimulation of macrophages and modulation The biologicalactivity of sulfur polysaccharides is linked to their sugarcomposition position and degree of sulfation [95] Amongthe microalgae capable of producing these compounds areChlorella vulgaris Scenedesmus quadricauda [96] and Por-phyridium sp [97]
52 Compounds with Antimicrobial Activity The importanceof discovering new compounds with antimicrobial activityis driven by the development of antibiotic resistance inhumans due to constant clinical use of antibioticsMicroalgaeare an important source of antibiotics with a broad andefficient antibacterial activity [11] The antimicrobial activityof these microorganisms is due to the ability to synthesizecompounds such as fatty acids acrylic acids halogenatedaliphatic compounds terpenoids sterols sulfur-containingheterocyclic compounds carbohydrates acetogenins andphenols [98]
The antimicrobial activity of extracts from microalgae isrelated to its lipid composition The antimicrobial action ofmicroalgae is also noteworthy because of the potential toproduce compounds such as 120572- and 120573-ionone 120573-cyclocitralneophytadiene and phytol [99] Microalgae antimicrobialactivity against human pathogens such as Escherichia coliPseudomonas aeruginosa Staphylococcus aureus and Staphy-lococcus epidermidis has been attributed to 120574-linolenic acid
The mechanism of action of fatty acids affects variousstructures in microorganisms however cell membranes arethe most impacted Membrane damage most likely leadsto a loss of internal substances from the cells and theentry of harmful components reduces nutrient absorption inaddition to inhibiting cellular respiration The ability of fattyacids to interfere with bacterial growth depends on boththeir chain length and the degree of unsaturation Fatty acidswith more than 10 carbon atoms apparently induce lysis ofbacterial protoplasts [99]
Microbial polysaccharides and other biological com-pounds have antiviral and antimicrobial action Microalgaeproduce extracellular sulfated polysaccharide (EPS) withacidic characteristics that has a potential as a therapeuticagent [101] Highly sulfated antiviral polysaccharides fromseveral species of microalgae consist mainly of xylose glu-cose and galactose The EPS sulfate groups determine somecharacteristics of polysaccharides it has been found thathigher sulphate contents induced higher antiviral activities[94 101] The inhibitory effect of polysaccharides of microal-gal origin is due to viral interactions or positive charges onthe cell surface thereby preventing penetration of the virusinto host cells [99]
The cyanobacterium Spirulina (Arthrospira) can producesulfated polysaccharides that have already found applicationsas antiviral agents both in vivo and in vitro [102] Eukaryoticmicroalgae such as Chlorella sp and Dunaliella sp produceand secrete polysaccharides at relatively high levels [17] Theantibacterial ability of Spirulina has been correlated withtheir volatile composition resulting in the identification of15 elements which constitutes 96 of total compounds Themajor volatile components produced by Spirulina consist ofheptadecane (40) and tetradecane (35) [39]
Some studies have reported that sulfated polysaccharidesderived from microalgae inhibit viral infection such asencephalomyocarditis virus Herpes simplex virus types 1and 2 (HSV1 HSV2) human immunodeficiency virus (HIV)hemorrhagic septicemia in salmonid virus swine fever virusand varicella virus [99 103] Carrageenan is a sulfatedpolysaccharide that can directly bind to human papillo-mavirus to inhibit not only the viral adsorption process butalso the input and subsequent process of the uncoating of thevirus [101]
53 Compounds with Anti-Inflammatory Action Inflam-mation is an immediate reaction to a cell or tissueinjury caused by noxious stimuli such as toxins andpathogens In this situation the body recognizes theagents responsible for the attack and attempts to neu-tralize them as quickly as possible Inflammation causesredness swelling heat and pain usually located at thesite of infection [104] Ingestion of anti-inflammatory com-pounds enhances the bodyrsquos immune response and helpsto prevent disease and aids the healing process Microal-gae produce several anti-inflammatory compounds in their
BioMed Research International 9
biomass that may exert a protective function in the bodywhen consumed as food or used as pharmaceuticals andcosmetics
Because of its anti-inflammatory capabilities microalgalbiomass is being considered for applications in tissue engi-neering for the development of scaffolds for use in reconsti-tution of organs and tissues [105 106] This is an importantapplication for humans especially in patients with burnsin which the skin was completely lost [107] Among themost important microalgal compounds with such prop-erties are long-chain polyunsaturated fatty acids (PUFAs)[108 109] sulfurized polysaccharides [110] and pigments[111]
Many microalgal polysaccharides possess the ability tomodulate the immune system through the activation ofmacrophage functions and the induction of reactive oxy-gen species (ROS) nitric oxide (NO) and various othertypes of cytokineschemokines [112] Macrophages are ableto regulate several innate responses and secrete cytokinesand chemocytokines that serve as signals for immune andinflammatory molecular reactions [113] Sulfur polysaccha-rides with anti-inflammatory activity can be applied inskin treatments inhibiting the migration and adhesion ofpolymorphonuclear leukocytes [110] Guzman et al [114]studied the anti-inflammatory capacity of the microalgaChlorella stigmatophora and Phaeodactylum tricomutum andconcluded that bothmicroalgae showed positive responses inthe test of paw edema by carrageenan
The PUFAs especially 1205963 and 1205966 as eicosapentaenoic(EPA) docosahexaenoic (DHA) and arachidonic (AA) acidshave been applied in the treatment of chronic inflammationsuch as rheumatism and skin diseases [108] Ryckebosch etal [115] evaluated the nutritional value of the total lipidsextracted from different PUFAs produced by microalgae Inthis study the microalgae IsochrysisNannochloropsis Phaeo-dactylum Pavlova and Thalassiosira produced 1205963 PUFA asan alternative to fish oil in food
Among the pigments with anti-inflammatory activityfucoxanthin carotenoid found in diatoms [116 117] is capableof stimulating apoptosis in human cancer cells [118] A phy-cocyanin found in cyanobacteria has an anti-inflammatoryactivity that occurs through the inhibition of histaminerelease [111 119]
54 Compounds with Potentiality over Degenerative Dis-eases In humans the oxidation reactions driven by reactiveoxygen species (ROS) can lead to irreversible damage tocellular components including lipids proteins and DNAdegradation andor mutation Consequently this damagecan lead to several syndromes such as cardiovascular dis-ease some cancers and the degenerative diseases of aging[120]
Chronic age-related diseases involve oxidative stress andinflammation and their consequences Chronic inflammationplays a significant role in the mediation of neurodegenerativediseases such as Parkinsonrsquos disease Alzheimerrsquos diseasemultiple sclerosis acquired immunodeficiency syndrome(AIDS) and dementia complex [77]
Natural pigments derived from microalgae (NPs) haveneuroprotective properties being valuable sources as func-tional ingredients in foods and pharmaceutical products thatshow efficient action in the treatment andor prevention ofneurodegenerative diseases Vitamin E has preventive effectsfor many diseases such as atherosclerosis and heart diseaseas well as neurodegenerative diseases such as multiplesclerosis [77]
Carotenoids have great potential benefits to humanhealth including the treatment of degenerative diseases suchas macular degeneration and cataract development Thesecompounds act as antioxidants reducing oxidative damageby ROS Studies indicated that increased intake of phenolsdecreased the occurrence of degenerative diseases Phenoliccompounds from microalgae with the potential to fight freeradicals have been reported [121]
Dunaliella salina is a natural source of 120573-carotene whichproduced a reduced risk of cancer and degenerative diseasesin humans Lutein is effective against various diseases includ-ing cataracts and macular degeneration and in the earlystages of atherosclerosis Extracts of Chlorella sp containing120573-carotene and lutein significantly prevented the cognitivedisability that accompanies Alzheimerrsquos disease in rats It wasalso reported that lutein extracted from Chlorella reducedthe incidence of cancer Likewise carotenoids extractedfrom Chlorella ellipsoidea and Chlorella vulgaris inhibited thegrowth of colon cancer [122] A lycopene extracted fromthe microalgae Chlorella marina significantly reduced theproliferation of prostate cancer inmice [123]This compoundalso reduced total cholesterol and low-density lipoprotein(LDL) levels [123] and improved rheumatoid arthritis [124]
Low plasma levels of lutein have also been associatedwith an increased tendency ofmyocardial infarction whereashigh intake of lutein was related to a decreased risk ofstroke In addition high levels of carotenoids with provi-tamin A activity including 120572-carotene 120573-carotene and 120573-cryptoxanthin have been associated with reduction in therisk of angina pectoris Macular degeneration the lead-ing cause of irreversible vision loss has also been associ-ated with very low consumption of lutein and zeaxanthin[125]
Scientific findings indicate astaxanthin for multimodalintervention formany forms of degenerative diseases includ-ing cardiovascular diseases cancer metabolic syndromecognitive impairment age-related immune dysfunctionstomach and ocular diseases (macular degeneration cataractglaucoma diabetic retinopathy and retinitis pigmentosa)and skin damage [126] High levels of lycopene in plasmaand tissues were inversely related to coronary heart diseasemyocardial infarction and the risk of atherosclerosis [125]
55 Compounds withHealth Promoting Function The impor-tance of microalgae as sources of functional ingredients hasbeen recognized because of their beneficial health effectsNatural pigments are valuable sources of bioactive com-pounds These pigments have various beneficial biologicalactivities such as antioxidant anticancer anti-inflammatoryantiobesity antiangiogenic and neuroprotective action and
10 BioMed Research International
are indicated for the treatment or prevention of severalchronic diseases [77]
The antioxidant potential of carotenoid pigments andtheir ability to prevent cancer aging atherosclerosis coro-nary heart disease and degenerative diseases have beendescribed 120573-Carotene has higher provitamin A activitywhich is essential for vision and the correct functioning ofthe immune system Astaxanthin is linked to many healthbenefits such as protection against lipid peroxidation age-related macular degeneration reduced atherosclerosis andan increased immune response [102]
Fucoxanthin is considered as a promising dietary andweight loss supplement and for the treatment of obesityClinical studies by Abidov et al [127] demonstrated the effectof ldquoxanthigenrdquo a fucoxanthin based antiobesity supplementFurthermore fucoxanthinmay be useful for the prevention ofbone diseases such as osteoporosis and rheumatoid arthritisIt has also been reported to be effective for the therapeutictreatment of diabetic diseases suppressing insulin and hyper-glycemia [77]
Microalgae proteins are of great interest as a source ofbioactive peptides due to their therapeutic potential in thetreatment of various diseases [7] Proteins peptides andamino acids have functions that contribute to health benefitsThese compounds can include growth factors hormones andimmunomodulators and can help to replace damaged tissuesin addition to providing nutritional benefits Microalgaesuch as Chlorella and Spirulina (Arthrospira) may be usedas nutraceuticals or included in functional foods to preventdiseases and damage to cells and tissues due to their richprotein content and amino acid profile [102]
The antimicrobial action of certain enzymes (eglysozyme) and immunoglobulins has been reported andrecommended for people with different diseases (egCrohnrsquos disease) due to the existence of formulations withpeptides and free amino acids Studies of the healtheffects of lysozyme have been reported in the microalgaeSpirulina platensis [128] Chlorella [129] and Dunaliellasalina [130] Spirulina (Arthrospira) and Chlorella biomasspills are marketed as is ldquoHawaiian Spirulina Pacificardquo(httpspirulinagreennutritionalscomau) Other proteinscan also increase the production of cholecystokinin involvedin appetite suppression and the reduction of LDL-cholesterolProtein peptides from Chlorella have a potential as dietarysupplements for the prevention of oxidative stress-relateddiseases such as atherosclerosis coronary heart disease andcancer [39]
The essential fatty acids 120596-3 and 120596-6 in particular areimportant for the integrity of tissues 120574-Linolenic acid hastherapeutic applications in cosmetics to revitalize the skinand thus slow aging Linoleic and linolenic acids are essentialnutrients for the immune system and other related tissueregeneration processes Linoleic acid is also used for thetreatment of hyperplasia of the skin [102]
The most studied microalgal lipid compounds are thepolyunsaturated fatty acids (PUFAs) docosahexaenoic acid(120596-3 C226) (DHA) eicosapentaenoic acid (C20 120596-35)(EPA) and arachidonic acid (120596-6 C204) (ARA) Studies haveshown that dietary120596-3 PUFAs have a protective effect against
atherosclerotic heart disease [131] DHA and EPA showed theability to reduce problems associated with strokes and arthri-tis besides reducing hypertension lipid content (a decreasein triglycerides and an increase of HDL) and acting asanti-inflammatory agents DHA is also important in thedevelopment and function of the nervous system Further-more ARA and EPA are platelet aggregators vasoconstric-tors and vasodilators and have antiaggregative action on theendothelium as well as chemostatic activity in neutrophils[102]
Other lipid compounds with interesting bioactive prop-erties are the microalgal sterols Phytosterols have demon-strated reduction of total cholesterol (LDL) in humans byinhibiting its absorption from the intestine [50] Polysac-charides can be considered as dietary fibers associatedwith different physiological effects Insoluble fiber (cellulosehemicellulose and lignin) mainly promotes the movementof material through the digestive system thereby improvinglaxation and increasing satietyThey can also be considered asprebiotics because they promote the growth of gutmicrofloraincluding probiotic species Soluble fiber (oligosaccharidespectins and 120573-glucans) may reduce cholesterol and regulateblood glucose [7 132]
6 Conclusion
The proven ability of microalgae to produce bioactive com-pounds places these microorganisms in the biotechnologicalspotlight for applications in various areas of study especiallyin the life sciencesThe production ofmicroalgal metaboliteswhich stimulate defense mechanisms in the human bodyhas spurred intense study of the application of microalgalbiomass in various foods and pharmacological and medicalproducts There is obviously a need for further study of theidentified compounds and their activities in the treatmentand prevention of various diseases in addition to an ongoingsearch for other as yet undetected metabolites
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgment
The authors thank the National Counsel of Technologicaland Scientific Development (CNPq) for the Productivityin Technological Development and Innovative ExtensionScholarship
References
[1] S P Ferreira L A Soares and J A Costa ldquoMicroalgas umafonte alternativa na obtencao de acidos gordos essenciaisrdquoRevista de Ciencias Agrarias vol 36 pp 275ndash287 2013
[2] A A El Gamal ldquoBiological importance of marine algaerdquo SaudiPharmaceutical Journal vol 18 no 1 pp 1ndash25 2010
BioMed Research International 11
[3] I Moreno-Garrido ldquoMicroalgae immobilization current tech-niques and usesrdquo Bioresource Technology vol 99 no 10 pp3949ndash3964 2008
[4] R-B Volk and F H Furkert ldquoAntialgal antibacterial andantifungal activity of two metabolites produced and excretedby cyanobacteria during growthrdquoMicrobiological Research vol161 no 2 pp 180ndash186 2006
[5] R-B Volk ldquoA newly developed assay for the quantitativedetermination of antimicrobial (anticyanobacterial) activity ofboth hydrophilic and lipophilic test compounds without anyrestrictionrdquoMicrobiological Research vol 163 no 2 pp 161ndash1672008
[6] D F Smee K W Bailey M-H Wong et al ldquoTreatment ofinfluenza A (H1N1) virus infections in mice and ferrets withcyanovirin-Nrdquo Antiviral Research vol 80 no 3 pp 266ndash2712008
[7] E Ibanez and A Cifuentes ldquoBenefits of using algae as naturalsources of functional ingredientsrdquo Journal of the Science of Foodand Agriculture vol 93 no 4 pp 703ndash709 2013
[8] G Markou and E Nerantzis ldquoMicroalgae for high-valuecompounds and biofuels production a review with focus oncultivation under stress conditionsrdquo Biotechnology Advancesvol 31 no 8 pp 1532ndash1542 2013
[9] R Harun M Singh G M Forde andM K Danquah ldquoBiopro-cess engineering ofmicroalgae to produce a variety of consumerproductsrdquo Renewable and Sustainable Energy Reviews vol 14no 3 pp 1037ndash1047 2010
[10] C Kolympiris N Kalaitzandonakes and D Miller ldquoPublicfunds and local biotechnology firm creationrdquo Research Policyvol 43 no 1 pp 121ndash137 2014
[11] S Bhagavathy P Sumathi and I Jancy Sherene Bell ldquoGreenalgae Chlorococcum humicola-a new source of bioactive com-pounds with antimicrobial activityrdquo Asian Pacific Journal ofTropical Biomedicine vol 1 no 1 pp S1ndashS7 2011
[12] A M F Palavra J P Coelho J G Barroso et al ldquoSupercrit-ical carbon dioxide extraction of bioactive compounds frommicroalgae and volatile oils from aromatic plantsrdquo Journal ofSupercritical Fluids vol 60 pp 21ndash27 2011
[13] I Priyadarshani and B Rath ldquoCommercial and industrialapplications of micro algaemdasha reviewrdquo Journal of Algal BiomassUtilization vol 3 no 4 pp 89ndash100 2012
[14] JW Blunt B R CoppM H GMunro P T Northcote andMR Prinsep ldquoMarine natural productsrdquoNatural Product Reportsvol 23 no 1 pp 26ndash78 2006
[15] A M S Mayer and M T Hamann ldquoMarine pharmacologyin 2001-2002 marine compounds with anthelmintic antibacte-rial anticoagulant antidiabetic antifungal anti-inflammatoryantimalarial antiplatelet antiprotozoal antituberculosis andantiviral activities affecting the cardiovascular immune andnervous systems and other miscellaneous mechanisms ofactionrdquo Comparative Biochemistry and Physiology Part C Toxi-cology amp Pharmacology vol 140 no 3-4 pp 265ndash286 2005
[16] M Plaza S Santoyo L Jaime et al ldquoScreening for bioactivecompounds from algaerdquo Journal of Pharmaceutical and Biomed-ical Analysis vol 51 no 2 pp 450ndash455 2010
[17] I Rodrıguez-Meizoso L Jaime S Santoyo et al ldquoPressurizedfluid extraction of bioactive compounds from Phormidiumspeciesrdquo Journal of Agricultural and Food Chemistry vol 56 no10 pp 3517ndash3523 2008
[18] L R Carvalho A Costa-Neves G A A Conserva et alldquoBiologically active compounds from cyano bacteria extracts in
vivo and in vitro aspectsrdquo Brazilian Journal of Pharmacognosyvol 23 no 3 pp 471ndash480 2013
[19] B Nobre FMarcelo R Passos et al ldquoSupercritical carbon diox-ide extraction of astaxanthin and other carotenoids from themicroalga Haematococcus pluvialisrdquo European Food Researchand Technology vol 223 no 6 pp 787ndash790 2006
[20] R L Mendes A D Reis and A F Palavra ldquoSupercritical CO2
extraction of 120574-linolenic acid and other lipids from Arthrospira(Spirulina)maxima comparison with organic solvent extrac-tionrdquo Food Chemistry vol 99 no 1 pp 57ndash63 2006
[21] I Romano M R Bellitti B Nicolaus et al ldquoLipid profilea useful chemotaxonomic marker for classification of a newcyanobacterium in Spirulina genusrdquo Phytochemistry vol 54 no3 pp 289ndash294 2000
[22] J A C Costa and M G Morais ldquoMicroalgae for food produc-tionrdquo in Fermentation Process Engineering in the Food IndustryC R Soccol A Pandey and C Larroche Eds p 486 Taylor ampFrancis 2013
[23] MAAmbrosi CO Reinehr T E Bertolin et al ldquoPropriedadesde saude de Spirulina spprdquo Revista de Ciencias FarmaceuticasBasica e Aplicada vol 29 no 2 pp 109ndash117 2008
[24] J A Borges G M Rosa L H R Meza A A Henrard M RA Z Souza and J A V Costa ldquoSpirulina sp LEB-18 cultureusing effluent from the anaerobic digestionrdquo Brazilian Journalof Chemical Engineering vol 30 no 2 pp 277ndash287 2013
[25] F S Antelo J A V Costa and S J Kalil ldquoThermal degradationkinetics of the phycocyanin from Spirulina platensisrdquo Biochem-ical Engineering Journal vol 41 no 1 pp 43ndash47 2008
[26] S T Silveira J F M Burkert J A V Costa C A V Burkertand S J Kalil ldquoOptimization of phycocyanin extraction fromSpirulina platensis using factorial designrdquo Bioresource Technol-ogy vol 98 no 8 pp 1629ndash1634 2007
[27] L M Colla C O Reinehr C Reichert and J A V Costa ldquoPro-duction of biomass and nutraceutical compounds by Spirulinaplatensis under different temperature and nitrogen regimesrdquoBioresource Technology vol 98 no 7 pp 1489ndash1493 2007
[28] R P Rastogi and R P Sinha ldquoBiotechnological and industrialsignificance of cyanobacterial secondary metabolitesrdquo Biotech-nology Advances vol 27 no 4 pp 521ndash539 2009
[29] N A E Semary ldquoThe characterisation of bioactive compoundsfrom an Egyptian Leptolyngbya sp strainrdquo Annals of Microbiol-ogy vol 62 no 1 pp 55ndash59 2012
[30] L M Colla A L Muccillo-Baisch and J A Vieira CostaldquoSpirulina platensis effects on the levels of total cholesterol HDLand triacylglycerols in rabbits fed with a hypercholesterolemicdietrdquo Brazilian Archives of Biology and Technology vol 51 no 2pp 405ndash411 2008
[31] P V Torres-Duran A Ferreira-Hermosillo and M A Juarez-Oropeza ldquoAntihyperlipemic and antihypertensive effects ofSpirulina maxima in an open sample of Mexican population apreliminary reportrdquo Lipids in Health and Disease vol 6 article33 2007
[32] S AnshumanMDeepikaG Sharmila andCMuthukumaranldquoEffect of glucose and phytohaemagglutinin (PHA) richPhaseo-lus vulgaris extract on growth and protein synthesis of pharma-ceutically important cyanobacteriaNostoc ellipsosporumNCIM2786rdquo Journal of Genetic Engineering and Biotechnology vol 11no 1 pp 33ndash37 2013
[33] IMaldener andAMMuro-PasterEncyclopedia of Life Sciences(ELS) John Wiley amp Sons Chichester UK 2010
12 BioMed Research International
[34] M Temina H Rezankova T Rezanka and V M DembitskyldquoDiversity of the fatty acids of the Nostoc species and theirstatistical analysisrdquoMicrobiological Research vol 162 no 4 pp308ndash321 2007
[35] Z Deng Q Hu F Lu G Liu and Z Hu ldquoColony developmentand physiological characterization of the edible blue-greenalga Nostoc sphaeroides (Nostocaceae Cyanophyta)rdquo Progressin Natural Science vol 18 no 12 pp 1475ndash1484 2008
[36] M R Boyd K R Gustafson J B McMahon et al ldquoDiscoveryof cyanovirin-N a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycopro-tein gp120 potential applications to microbicide developmentrdquoAntimicrobial Agents and Chemotherapy vol 41 no 7 pp 1521ndash1530 1997
[37] M Wang Y-N Xu G-Z Jiang L-B Li and T-Y KuangldquoMembrane lipids and their fatty acid composition in Nostocflagelliforme cellsrdquoActa Botanica Sinica vol 42 no 12 pp 1263ndash1266 2000
[38] J Masojıdek and O Prasil ldquoThe development of microalgalbiotechnology in the Czech Republicrdquo Journal of IndustrialMicrobiology amp Biotechnology vol 37 no 12 pp 1307ndash1317 2010
[39] M Plaza M Herrero A Alejandro Cifuentes and E IbanezldquoInnovative natural functional ingredients from microalgaerdquoJournal of Agricultural and Food Chemistry vol 57 no 16 pp7159ndash7170 2009
[40] J A V Costa E M Radmann V S Cerqueira G C Santosand M N Calheiros ldquoPerfil de acidos graxos das microalgasChlorella vulgaris e Chlorella minutissima cultivadas em difer-entes condicoesrdquo Alimentos e Nutricao Araraquara vol 17 no4 pp 429ndash436 2006
[41] K H Cha S W Kang C Y Kim B H Um Y R Naand C-H Pan ldquoEffect of pressurized liquids on extraction ofantioxidants from chlorella vulgarisrdquo Journal of Agricultural andFood Chemistry vol 58 no 8 pp 4756ndash4761 2010
[42] F Kokou P Makridis M Kentouri and P Divanach ldquoAntibac-terial activity inmicroalgae culturesrdquoAquaculture Research vol43 no 10 pp 1520ndash1527 2012
[43] L Li W Li Y-H Kim and YW Lee ldquoChlorella vulgaris extractameliorates carbon tetrachloride-induced acute hepatic injuryin micerdquo Experimental and Toxicologic Pathology vol 65 no 1-2 pp 73ndash80 2013
[44] N B Medina-Jaritz L F Carmona-Ugalde J C Lopez-CedilloandF S L Ruiloba-DeLeon ldquoAntibacterial activity ofmethano-lic extracts from Dunaliella salina and Chlorella vulgarisrdquo TheFASEB Journal vol 27 abstract 11675 2013
[45] L Zhao and B V Sweet ldquoLutein and zeaxanthin for maculardegenerationrdquo The American Journal of Health-System Phar-macy vol 65 no 13 pp 1232ndash1238 2008
[46] P Spolaore C Joannis-Cassan E Duran and A IsambertldquoCommercial applications of microalgaerdquo Journal of Bioscienceand Bioengineering vol 101 no 2 pp 87ndash96 2006
[47] C Rosch and C Posten ldquoChallenges and perspectives ofmicroalgae productionrdquo TechnikfolgenabschatzungmdashTheorieund Praxis vol 21 no 1 2012
[48] K Preetha L John C S Subin and K K Vijayan ldquoPhenotypicand genetic characterization of Dunaliella (Chlorophyta) fromIndian salinas and their diversityrdquoAquatic Biosystems vol 8 no1 article 27 2012
[49] A Hosseini Tafreshi and M Shariati ldquoDunaliella biotechnol-ogy methods and applicationsrdquo Journal of Applied Microbiol-ogy vol 107 no 1 pp 14ndash35 2009
[50] M Francavilla P Trotta and R Luque ldquoPhytosterols fromDunaliella tertiolecta and Dunaliella salina a potentially novelindustrial applicationrdquo Bioresource Technology vol 101 no 11pp 4144ndash4150 2010
[51] F F Madkour and M M Abdel-Daim ldquoHepatoprotective andantioxidant activity of dunaliella salina in paracetamol-inducedacute toxicity in ratsrdquo Indian Journal of Pharmaceutical Sciencesvol 75 no 6 pp 642ndash648 2013
[52] T Chang S Ohta N Ikegami H Miyata T Kashimoto andM Kondo ldquoAntibiotic substances produced by a marine greenalgaDunaliella primolectardquo Bioresource Technology vol 44 no2 pp 149ndash153 1993
[53] M Herrero L Jaime P J Martın-Alvarez A Cifuentes and EIbanez ldquoOptimization of the extraction of antioxidants fromDunaliella salina microalga by pressurized liquidsrdquo Journal ofAgricultural and Food Chemistry vol 54 no 15 pp 5597ndash56032006
[54] R Leon M Martın J Vigara C Vilchez and J MVega ldquoMicroalgae mediated photoproduction of 120573-carotene inaqueous-organic two phase systemsrdquo Biomolecular Engineeringvol 20 no 4ndash6 pp 177ndash182 2003
[55] M Garcıa-Gonzalez J Moreno J C Manzano F J Florencioand M G Guerrero ldquoProduction of Dunaliella salina biomassrich in 9-119888119894119904-120573-carotene and lutein in a closed tubular photo-bioreactorrdquo Journal of Biotechnology vol 115 no 1 pp 81ndash902005
[56] D M M Kleinegris M Janssen W A Brandenburg andR H Wijffels ldquoContinuous production of carotenoids fromDunaliella salinardquo Enzyme and Microbial Technology vol 48no 3 pp 253ndash259 2011
[57] P Stolz and B Obermayer ldquoManufacturing microalgae for skincarerdquo Cosmetics amp Toiletries Science Applied vol 120 pp 99ndash106 2005
[58] M N Noaman ldquoEffect of potassium and nitrogen fertilizers onthe growth and biomass of some halophytes grown under highlevels of salinityrdquo Journal of Agronomy vol 3 no 1 pp 25ndash302004
[59] S O Lourenco Cultivo de Microalgas Marinhas Princıpios eAplicacoes RiMa Sao Paulo Brazil 2006
[60] G E Fogg ldquoThe ecological significance of extracellular prod-ucts of phytoplankton photosynthesisrdquo Botanica Marina vol26 no 1 pp 3ndash14 1983
[61] D L Nelson and M M Cox Princıpios de Bioquımica SarvierSao Paulo Brazil 4th edition 2004
[62] T Chrismadha andM A Borowitzka ldquoEffect of cell density andirradiance on growth proximate composition and eicosapen-taenoic acid production of Phaeodactylum tricornutum grownin a tubular photobioreactorrdquo Journal of Applied Phycology vol6 no 1 pp 67ndash74 1994
[63] A C Guedes L A Meireles H M Amaro and F X MalcataldquoChanges in lipid class and fatty acid composition of culturesof Pavlova lutheri in response to light intensityrdquo Journal of theAmerican Oil Chemistsrsquo Society vol 87 no 7 pp 791ndash801 2010
[64] H K Madhyastha S Sivashankari and T M Vatsala ldquoC-phycocyanin from Spirulina fussiformis exposed to blue lightdemonstrates higher efficacy of in vitro antioxidant activityrdquoBiochemical Engineering Journal vol 43 no 2 pp 221ndash2242009
[65] A Vonshak Spirulina platensis (Athrospira) Physiology Cell-Biology and Biotechnoloby Taylor amp Francis London UK 1997
[66] R D Fox Spirulina Production amp Potential Edisud ParisFrance 1996
BioMed Research International 13
[67] C U Ugwu H Aoyagi and H Uchiyama ldquoPhotobioreactorsfor mass cultivation of algaerdquo Bioresource Technology vol 99no 10 pp 4021ndash4028 2008
[68] S V Mohan M V Rohit P Chiranjeevi R Chandra and BNavaneeth ldquoHeterotrophic microalgae cultivation to synergizebiodiesel production with waste remediation progress andperspectivesrdquo Bioresource Technology 2014
[69] M G Morais and J A C Costa ldquoAn open pond system formicroalgal cultivationinrdquo in Biofuels from Algae A Pandey D-J Lee Y Chisti and C R Soccol Eds p 1 Elsevier 2014
[70] R E Lee Phycology Cambridge University Press New YorkNY USA 1980
[71] A RichmondHandbook ofMicroalgalMass Culture CRCPressBoston Mass USA 1990
[72] M Coca V M Barrocal S Lucas G Gonzalez-Benito andM T Garcıa-Cubero ldquoProtein production in Spirulina platensisbiomass using beet vinasse-supplemented culture mediardquo Foodand Bioproducts Processing 2014
[73] P-F Ip and F Chen ldquoPeroxynitrite and nitryl chloride enhanceastaxanthin production by the green microalga Chlorella zofin-giensis in heterotrophic culturerdquo Process Biochemistry vol 40no 11 pp 3595ndash3599 2005
[74] D L Alonso E-H Belarbi J M Fernandez-Sevilla JRodrıguez-Ruiz and E M Grima ldquoAcyl lipid compositionvariation related to culture age and nitrogen concentration incontinuous culture of the microalga Phaeodactylum tricornu-tumrdquo Phytochemistry vol 54 no 5 pp 461ndash471 2000
[75] W Schmidell A U Lima E Aquarone and W BorzaniBiotecnologia Industrial Volume 2 Edgard Blucher Sao PauloBrazil 2001
[76] R R L Guillard ldquoCulture of phytoplankton for feeding marineinvertebratesrdquo in Culture of Marine Invertebrate Animals W LSmith and M H Chanley Eds pp 29ndash60 Plenum New YorkNY USA 1975
[77] R Pangestuti and S-K Kim ldquoBiological activities and healthbenefit effects of natural pigments derived from marine algaerdquoJournal of Functional Foods vol 3 no 4 pp 255ndash266 2011
[78] K Skjanes C Rebours and P Lindblad ldquoPotential for greenmicroalgae to produce hydrogen pharmaceuticals and otherhigh value products in a combined processrdquo Critical Reviews inBiotechnology vol 33 no 2 pp 172ndash215 2013
[79] I Rodrıguez-Meizoso L Jaime S Santoyo F J Senorans ACifuentes and E Ibanez ldquoSubcritical water extraction andcharacterization of bioactive compounds from Haematococcuspluvialis microalgardquo Journal of Pharmaceutical and BiomedicalAnalysis vol 51 no 2 pp 456ndash463 2010
[80] M Herrero M Castro-Puyana J A Mendiola and E IbanezldquoCompressed fluids for the extraction of bioactive compoundsrdquoTrends in Analytical Chemistry vol 43 pp 67ndash83 2013
[81] N K Singh and D W Dhar ldquoMicroalgae as second generationbiofuel A reviewrdquo Agronomy for Sustainable Development vol31 no 4 pp 605ndash629 2011
[82] L Brennan and P Owende ldquoBiofuels frommicroalgae towardsmeeting advanced fuel standardsrdquo in Advanced Biofuels andBioproducts JW Lee Ed pp 553ndash599 Springer NewYork NYUSA 2013
[83] A Singh P S Nigam and J D Murphy ldquoRenewable fuels fromalgae an answer to debatable land based fuelsrdquo BioresourceTechnology vol 102 no 1 pp 10ndash16 2011
[84] P Perez-Lopez S Gonzalez-Garcıa R G Ulloa J SineiroG Feijoo and M T Moreira ldquoLife cycle assessment of the
production of bioactive compounds from Tetraselmis suecica atpilot scalerdquo Journal of Cleaner Production vol 64 pp 323ndash3312014
[85] B Subhadra ldquoAlgal biorefinery-based industry an approachto address fuel and food insecurity for a carbon-smart worldrdquoJournal of the Science of Food and Agriculture vol 91 no 1 pp2ndash13 2011
[86] D J Newman and G M Cragg ldquoNatural products as sourcesof new drugs over the 30 years from 1981 to 2010rdquo Journal ofNatural Products vol 75 no 3 pp 311ndash335 2012
[87] H-B Li K-W Cheng C-C Wong K-W Fan F Chen andY Jiang ldquoEvaluation of antioxidant capacity and total phenoliccontent of different fractions of selected microalgaerdquo FoodChemistry vol 102 no 3 pp 771ndash776 2007
[88] T M Mata A A Martins and N S Caetano ldquoMicroalgaefor biodiesel production and other applications a reviewrdquoRenewable and Sustainable EnergyReviews vol 14 no 1 pp 217ndash232 2010
[89] A Gupta and J K Sainis ldquoIsolation of C-phycocyanin fromSynechococcus sp (Anacystis nidulans BD1)rdquo Journal of AppliedPhycology vol 22 no 3 pp 231ndash233 2010
[90] P J Viskari and C L Colyer ldquoRapid extraction of phyco-biliproteins from cultured cyanobacteria samplesrdquo AnalyticalBiochemistry vol 319 no 2 pp 263ndash271 2003
[91] R Bermejo Roman J M Alvarez-Pez F G Acien Fernandezand E Molina Grima ldquoRecovery of pure B-phycoerythrin fromthe microalga Porphyridium cruentumrdquo Journal of Biotechnol-ogy vol 93 no 1 pp 73ndash85 2002
[92] C I Cazzonelli ldquoCarotenoids in nature insights from plantsand beyondrdquo Functional Plant Biology vol 38 no 11 pp 833ndash847 2011
[93] M A Hejazi and R HWijffels ldquoMilking of microalgaerdquo Trendsin Biotechnology vol 22 no 4 pp 189ndash194 2004
[94] S Arad and O Levy-Ontman ldquoRed microalgal cell-wallpolysaccharides biotechnological aspectsrdquo Current Opinion inBiotechnology vol 21 no 3 pp 358ndash364 2010
[95] M Kim J H Yim S-Y Kim et al ldquoIn vitro inhibitionof influenza A virus infection by marine microalga-derivedsulfated polysaccharide p-KG03rdquoAntiviral Research vol 93 no2 pp 253ndash259 2012
[96] Z A Mohamed ldquoPolysaccharides as a protective responseagainst microcystin-induced oxidative stress in Chlorella vul-garis and Scenedesmus quadricauda and their possible signifi-cance in the aquatic ecosystemrdquo Ecotoxicology vol 17 no 6 pp504ndash516 2008
[97] T Tannin-Spitz M Bergman D Van-Moppes S Grossmanand S Arad ldquoAntioxidant activity of the polysaccharide of thered microalga Porphyridium sprdquo Journal of Applied Phycologyvol 17 no 3 pp 215ndash222 2005
[98] J W Prakash M Johnson and S Jeeva ldquoAntimicrobial activityof certain fresh water microalgae from Thamirabarani RiverTamil Nadu South Indiardquo Asian Pacific Journal of TropicalBiomedicine vol 1 supplement no 2 pp S170ndashS173 2011
[99] H M Amaro A C Guedes and F X Malcata ldquoAntimicrobialactivities of microalgae an invited reviewrdquo in Science againstMicrobial Pathogens Communicating Current Research andTechnological Advances A Mendez-Vilas Ed pp 1272ndash12802011
[100] V J Smith A PDesbois and E ADyrynda ldquoConventional andunconventional antimicrobials from fish marine invertebratesand micro-algaerdquo Marine Drugs vol 8 no 4 pp 1213ndash12622010
14 BioMed Research International
[101] M F D J Raposo A M M B de Morais and R M SC de Morais ldquoInfluence of sulphate on the composition andantibacterial and antiviral properties of the exopolysaccharidefrom Porphyridium cruentumrdquo Life Sciences vol 101 no 1-2 pp56ndash63 2014
[102] M F De Jesus Raposo R M S C De Morais and A M M BDe Morais ldquoHealth applications of bioactive compounds frommarine microalgaerdquo Life Sciences vol 93 no 15 pp 479ndash4862013
[103] A Smelcerovic Z Knezevic-Jugovic and Z PetronijevicldquoMicrobial polysaccharides and their derivatives as current andprospective pharmaceuticalsrdquo Current Pharmaceutical Designvol 14 no 29 pp 3168ndash3195 2008
[104] M T Madigan J M Martinko P V Dunlap and D P ClarkMicrobiologia de Brock Artmed Editora 12th edition 2010
[105] M G de Morais J A V Costa P H L Pranke et alldquoDevelopment of a newnanofiber scaffold for usewith stemcellsin a third degree burn animal modelrdquo Burns Oxford vol 40 no8 pp 1650ndash1660 2014
[106] M G de Morais C Stillings R Dersch et al ldquoPreparation ofnanofibers containing the microalga Spirulina (Arthrospira)rdquoBioresource Technology vol 101 no 8 pp 2872ndash2876 2010
[107] D Steffens M Lersch A Rosa et al ldquoA new biomaterialof nanofibers with the microalga Spirulina as scaffolds tocultivate with stem cells for use in tissue engineeringrdquo Journalof Biomedical Nanotechnology vol 9 no 4 pp 710ndash718 2013
[108] C Barrow and F ShahidiMarine Nutraceuticals and FunctionalFoods CRC Press Taylor amp Francis Boca Raton Fla USA2008
[109] M N A Khan J-Y ChoM-C Lee et al ldquoIsolation of two anti-inflammatory and one pro-inflammatory polyunsaturated fattyacids from the brown seaweed Undaria pinnatifidardquo Journal ofAgricultural and Food Chemistry vol 55 no 17 pp 6984ndash69882007
[110] M S Matsui N Muizzuddin S Arad and K MarenusldquoSulfated polysaccharides from redmicroalgae have antiinflam-matory properties in vitro and in vivordquo Applied Biochemistryand Biotechnology vol 104 no 1 pp 13ndash22 2003
[111] V B Bhat and K M Madyastha ldquoScavenging of peroxynitriteby phycocyanin and phycocyanobilin from Spirulina platensisprotection against oxidative damage to DNArdquo Biochemical andBiophysical Research Communications vol 285 no 2 pp 262ndash266 2001
[112] I A Schepetkin and M T Quinn ldquoBotanical polysaccharidesmacrophage immunomodulation and therapeutic potentialrdquoInternational Immunopharmacology vol 6 no 3 pp 317ndash3332006
[113] J K Park Z-H Kim C G Lee et al ldquoCharacterization andimmunostimulating activity of a water-soluble polysaccharideisolated from Haematococcus lacustrisrdquo Biotechnology and Bio-process Engineering vol 16 no 6 pp 1090ndash1098 2011
[114] S Guzman A Gato M Lamela M Freire-Garabal and J MCalleja ldquoAnti-inflammatory and immunomodulatory activitiesof polysaccharide from Chlorella stigmatophora and Phaeo-dactylum tricornutumrdquo Phytotherapy Research vol 17 no 6 pp665ndash670 2003
[115] E Ryckebosch C Bruneel R Termote-Verhalle K Goiris KMuylaert and I Foubert ldquoNutritional evaluation of microalgaeoils rich in omega-3 long chain polyunsaturated fatty acids as analternative for fish oilrdquo Food Chemistry vol 160 pp 393ndash4002014
[116] P Zhao Z Zang X Xie A Huang and G Wang ldquoTheinfluence of different flocculants on the physiological activityand fucoxanthin production of Phaeodactylum tricornutumrdquoProcess Biochemistry vol 49 no 4 pp 681ndash687 2014
[117] D Moreau C Tomasoni C Jacquot et al ldquoCultivated microal-gae and the carotenoid fucoxanthin from Odontella auritaas potent anti-proliferative agents in bronchopulmonary andepithelial cell linesrdquo Environmental Toxicology and Pharmacol-ogy vol 22 no 1 pp 97ndash103 2006
[118] H Maeda M Hosokawa T Sashima K Funayama and KMiyashita ldquoFucoxanthin from edible seaweed Undaria pinnati-fida shows antiobesity effect through UCP1 expression in whiteadipose tissuesrdquo Biochemical and Biophysical Research Commu-nications vol 332 no 2 pp 392ndash397 2005
[119] J E Piero Estrada P Bermejo Bescos and A M Villar delFresno ldquoAntioxidant activity of different fractions of Spirulinaplatensis protean extractrdquo IL Farmaco vol 56 no 5ndash7 pp 497ndash500 2001
[120] S-M Kang S-J Heo K-N Kim S-H Lee and Y-JJeon ldquoIsolation and identification of new compound 2710158401015840-phloroglucinol-661015840-bieckol from brown algae Ecklonia cavaand its antioxidant effectrdquo Journal of Functional Foods vol 4no 1 pp 158ndash166 2012
[121] HHAbdEl-Baky F K El Baz andG S El-Baroty ldquoProductionof phenolic compounds from Spirulinamaximamicroalgae andits protective effectsrdquoAfrican Journal of Biotechnology vol 8 no24 pp 7059ndash7067 2009
[122] A C Guedes H M Amaro and F X Malcata ldquoMicroalgae assources of carotenoidsrdquoMarineDrugs vol 9 no 4 pp 625ndash6442011
[123] G L Renju G M Kurup and K C H Saritha ldquoEffect oflycopene from Chlorella marina on high cholesterol-inducedoxidative damage and inflammation in ratsrdquo Inflammopharma-cology vol 22 no 1 pp 45ndash54 2014
[124] G L Renju G M Kurup and C H S Kumari ldquoAnti-inflammatory activity of lycopene isolated from Chlorellamarina onType II Collagen induced arthritis in SpragueDawleyratsrdquo Immunopharmacology and Immunotoxicology vol 35 no2 pp 282ndash291 2013
[125] C Vılchez E Forjan M Cuaresma F Bedmar I Garbayo andJ M Vega ldquoMarine carotenoids biological functions andcommercial applicationsrdquo Marine Drugs vol 9 no 3 pp 319ndash333 2011
[126] G Richardson ldquoBeyond eye healthrdquo Life Extension Magazine2011 httpwwwleforgMagazine20117Beyond-Eye-HealthPage-01
[127] M Abidov Z Ramazanov R Seifulla and S Grachev ldquoTheeffects of Xanthigen in the weight management of obesepremenopausal women with non-alcoholic fatty liver diseaseand normal liver fatrdquo Diabetes Obesity and Metabolism vol 12no 1 pp 72ndash81 2010
[128] H M Ragap R H Khalil and H HMutawie ldquoImmunostimu-lant effects of dietary Spirulina platensis on tilapia Oreochromisniloticusrdquo Journal of Applied Pharmaceutical Science vol 2 no2 pp 26ndash31 2012
[129] W Xu Z Gao Z Qi M Qiu J-Q Peng and R Shao ldquoEffect ofdietary chlorella on the growth performance and physiologicalparameters of gibel carp Carassius auratus gibeliordquo TurkishJournal of Fisheries and Aquatic Sciences vol 14 no 1 pp 53ndash572014
[130] P Amaninejad H Emadi M Ematiazjoo et al ldquoEffects ofDunaliella microalgae (Dunaliella salina) on different level of
BioMed Research International 15
IgM Immunoglobulin in rainbow trout (Oncrohynchusmykiss)rdquoGlobal Journal of Biodiversity Science and Management vol 3no 2 pp 237ndash242 2013
[131] V Mimouni L Ulmann V Pasquet et al ldquoThe potential ofmicroalgae for the production of bioactive molecules of phar-maceutical interestrdquoCurrent Pharmaceutical Biotechnology vol13 no 15 pp 2733ndash2750 2012
[132] S M Tosh and S Yada ldquoDietary fibres in pulse seeds and frac-tions characterization functional attributes and applicationsrdquoFood Research International vol 43 no 2 pp 450ndash460 2010
[133] H M Amaro R Barros A C Guedes I Sousa-Pinto and FXMalcata ldquoMicroalgal compoundsmodulate carcinogenesis inthe gastrointestinal tractrdquo Trends in Biotechnology vol 31 no 2pp 92ndash98 2013
[134] S S M Mostafa ldquoMicroalgal biotechnology prospects andapplicationsrdquo in Plant Science chapter 12 pp 275ndash314 InTech2012
[135] L Custodio T Justo L Silvestre et al ldquoMicroalgae of dif-ferent phyla display antioxidant metal chelating and acetyl-cholinesterase inhibitory activitiesrdquoFoodChemistry vol 131 no1 pp 134ndash140 2012
[136] C-CHu J-T Lin F-J Lu F-P Chou andD-J Yang ldquoDetermi-nation of carotenoids in Dunaliella salina cultivated in Taiwanand antioxidant capacity of the algal carotenoid extractrdquo FoodChemistry vol 109 no 2 pp 439ndash446 2008
Alonso et al [74] studying the influence of nitrogen con-centration in continuous cultivation on lipid concentrationin Phaeodactylum tricornutum noted that there was accu-mulation of saturated and unsaturated fatty acids when thenitrogen source was reduced
Culture media are chemical preparations that are formu-lated to contain the nutrients necessary for the microorgan-isms to multiply andor survive The culture media shouldmeet the nutritional needs of the microorganism assist inprocess control and have a reasonably fixed composition[75]
Among different microalgae variations in the culturemedium are mainly related to the amount of necessary nutri-ents Even so nutritional needs are dependent on environ-mental conditions [59] Microalgae require macronutrientssuch as C N O H P Ca Mg S and K for their growthThe micronutrients that are generally required are Fe MnCu Mo and Co Additionally some species require lowerconcentrations of vitamins in the culture medium [76]
4 Advantages of Using Microalgae to ObtainBioactive Compounds
Microalgae are important sources of bioactive natural sub-stances Many metabolites isolated from these microorgan-isms have shown biological activities and potential healthbenefits [77] Microalgae accumulate specific secondarymetabolites (such as pigments and vitamins) which are highvalue products that have applications in the cosmetic foodor pharmaceutical industries [8 78]
Microalgae live in complex habitats and are subjectedto stress andor extreme conditions such as changes insalinity temperature and nutrients Thus these microorgan-isms must rapidly adapt to new environmental conditions tosurvive and thus produce a great variety of biologically activesecondary metabolites that are not found in other organisms[79] Some of the advantages of microalgal cultivation maybe associated with taxonomic diversity the diverse chemicalcomposition the potential for growth in a bioreactor undercontrolled conditions and the ability to produce activesecondary metabolites in response to the stress induced byextreme exposure conditions [39 80]
In addition to their natural characteristics other impor-tant aspects related to microalgae are the use of solar energyand carbon dioxide (CO
2
) and a high growth rate whichcan produce higher yields compared to higher plants Inaddition microalgae can be grown in areas and climates thatare unsuitable for agriculture therefore microalgae do notcompete with arable food production land The possibility ofcontrolling the production of certain bioactive compoundsby manipulation of culture conditions is another advantageof using microalgae [7 81ndash83]
The cultivation of microalgae is a major mechanism forreducing excess carbon dioxide (CO
2
) in the atmosphere bybiofixation in which an industrial process uses a CO
2
-richgas as a carbon source formicroalgal growthThismechanismcontributes to a reduction of the greenhouse effect and globalwarming further reducing the costs of the carbon source
for growth which is the greatest nutrient requirement formicroalgae [13 84]
The cultivation of microalgae is not seasonal they areimportant for food in aquaculture systems and can effectivelyremove pollutants such as nitrogen and phosphorus fromwastewater Moreover they are themost efficient solar energybiomass converters Microalgae cultivation via sunlight-dependent systems contributes to sustainable developmentand natural resource management [13]
The integration of the production process of bioactivemetabolites in a biorefinery is a sustainable means of energyproduction food production and the production of productswith high added value [7] The biorefinery concept based onmicroalgae depends on the efficient use of biomass throughfractionation resulting in several isolated productsThis con-cept encompasses a biorefinery platform which is capable ofoffering a wide variety of different products such as productswith applications in pharmaceuticals medicine food (pro-tein fiber) and biofuels [7 85] These benefits contribute tothe economic viability of microalgal production [7 8]
5 Bioactive Compounds
Bioactive compounds are physiologically active substanceswith functional properties in the human body There is greatenthusiasm for the development and manufacture of variousbiocompounds that can potentially be used as functionalingredients such as carotenoids phycocyanins polyphenolsfatty acids and polyunsaturated compounds [16]
An interest in the production of bioactive compoundsfrom natural sources has recently emerged driven by agrowing number of scientific studies that demonstrate thebeneficial effects of these compounds on health [80] Naturalproducts are important in the search for new pharmaco-logically active compounds In general they play a role indrug discovery for the treatment of human diseases [86]Many clinically viable and commercially available drugs withantitumor and antiinfective activity originated as naturalproducts
Microalgae are a natural source of interesting biocom-pounds Microalgae are known to produce various therapeu-tically effective biocompounds that can be obtained from thebiomass or released extracellularly into the medium [11]These microorganisms contain many bioactive compoundssuch as proteins polysaccharides lipids vitamins enzymessterols and other high-value compounds with pharmaceu-tical and nutritional importance that can be employed forcommercial use [13]
51 Compounds with Antioxidant Function Oxidative dam-age caused by reactive oxygen species to lipids proteins andnucleic acids can cause many chronic diseases such as heartdisease atherosclerosis cancer and aging Epidemiologicalstudies have demonstrated an inverse association between theintake of fruits and vegetables and mortality from diseasessuch as cancer This phenomenon can be attributed to theantioxidant activity of these foods [87]
8 BioMed Research International
Microalgal biomass is considered a rich natural source ofantioxidants with potential applications in food cosmet-ics and medicine [87] Antioxidant compounds such asdimethylsulfoniopropionate and mycosporine amino acidswere isolated frommicroalgae and are potent chemical block-ers ofUV radiation [88] In addition to these compounds pig-ments lipids and polysaccharides with antioxidant activitycan also be found in microalgal biomass
Carotenoids and phycocyanins are the pigments mostused in scientific research C-phycocyanin (C-PC) is a bluephotosynthetic pigment that belongs to the group of phyco-biliproteins found in large quantities in the cyanobacteriaRhodophyta and Cryptophyte [89] Phycocyanin has appli-cations as a nutrient and natural food colorants and cosmet-ics It is usually extracted from the biomass of Spirulina [90]and Porphyridium cruentum [91] and Synechococcus [89]
Among the carotenoid compounds 120573-carotene andastaxanthin are prominent These compounds have appli-cation in the food and pharmaceutical industries becauseof their antioxidant properties and pigmentation ability Inmicroalgal metabolism they protect photosynthetic tissuesagainst damage caused by light and oxygen [92] Dunaliellasalina is a microalga recognized as a major biological sourceof 120573-carotene pigment producing more than 14 in drybiomass [46] H pluvialis is a source of the pigment astax-anthin producing 1ndash8 of astaxanthin as dry biomass [93]
Polysaccharides represent a class of high value-addedcomponents with applications in food cosmetics fabrics sta-bilizers emulsifiers and medicine [94] Microalgal polysac-charides contain sulphate esters are referred to as sulfatedpolysaccharides and possess unique medical applicationsThe basic mechanism of therapeutic action is based on thestimulation of macrophages and modulation The biologicalactivity of sulfur polysaccharides is linked to their sugarcomposition position and degree of sulfation [95] Amongthe microalgae capable of producing these compounds areChlorella vulgaris Scenedesmus quadricauda [96] and Por-phyridium sp [97]
52 Compounds with Antimicrobial Activity The importanceof discovering new compounds with antimicrobial activityis driven by the development of antibiotic resistance inhumans due to constant clinical use of antibioticsMicroalgaeare an important source of antibiotics with a broad andefficient antibacterial activity [11] The antimicrobial activityof these microorganisms is due to the ability to synthesizecompounds such as fatty acids acrylic acids halogenatedaliphatic compounds terpenoids sterols sulfur-containingheterocyclic compounds carbohydrates acetogenins andphenols [98]
The antimicrobial activity of extracts from microalgae isrelated to its lipid composition The antimicrobial action ofmicroalgae is also noteworthy because of the potential toproduce compounds such as 120572- and 120573-ionone 120573-cyclocitralneophytadiene and phytol [99] Microalgae antimicrobialactivity against human pathogens such as Escherichia coliPseudomonas aeruginosa Staphylococcus aureus and Staphy-lococcus epidermidis has been attributed to 120574-linolenic acid
The mechanism of action of fatty acids affects variousstructures in microorganisms however cell membranes arethe most impacted Membrane damage most likely leadsto a loss of internal substances from the cells and theentry of harmful components reduces nutrient absorption inaddition to inhibiting cellular respiration The ability of fattyacids to interfere with bacterial growth depends on boththeir chain length and the degree of unsaturation Fatty acidswith more than 10 carbon atoms apparently induce lysis ofbacterial protoplasts [99]
Microbial polysaccharides and other biological com-pounds have antiviral and antimicrobial action Microalgaeproduce extracellular sulfated polysaccharide (EPS) withacidic characteristics that has a potential as a therapeuticagent [101] Highly sulfated antiviral polysaccharides fromseveral species of microalgae consist mainly of xylose glu-cose and galactose The EPS sulfate groups determine somecharacteristics of polysaccharides it has been found thathigher sulphate contents induced higher antiviral activities[94 101] The inhibitory effect of polysaccharides of microal-gal origin is due to viral interactions or positive charges onthe cell surface thereby preventing penetration of the virusinto host cells [99]
The cyanobacterium Spirulina (Arthrospira) can producesulfated polysaccharides that have already found applicationsas antiviral agents both in vivo and in vitro [102] Eukaryoticmicroalgae such as Chlorella sp and Dunaliella sp produceand secrete polysaccharides at relatively high levels [17] Theantibacterial ability of Spirulina has been correlated withtheir volatile composition resulting in the identification of15 elements which constitutes 96 of total compounds Themajor volatile components produced by Spirulina consist ofheptadecane (40) and tetradecane (35) [39]
Some studies have reported that sulfated polysaccharidesderived from microalgae inhibit viral infection such asencephalomyocarditis virus Herpes simplex virus types 1and 2 (HSV1 HSV2) human immunodeficiency virus (HIV)hemorrhagic septicemia in salmonid virus swine fever virusand varicella virus [99 103] Carrageenan is a sulfatedpolysaccharide that can directly bind to human papillo-mavirus to inhibit not only the viral adsorption process butalso the input and subsequent process of the uncoating of thevirus [101]
53 Compounds with Anti-Inflammatory Action Inflam-mation is an immediate reaction to a cell or tissueinjury caused by noxious stimuli such as toxins andpathogens In this situation the body recognizes theagents responsible for the attack and attempts to neu-tralize them as quickly as possible Inflammation causesredness swelling heat and pain usually located at thesite of infection [104] Ingestion of anti-inflammatory com-pounds enhances the bodyrsquos immune response and helpsto prevent disease and aids the healing process Microal-gae produce several anti-inflammatory compounds in their
BioMed Research International 9
biomass that may exert a protective function in the bodywhen consumed as food or used as pharmaceuticals andcosmetics
Because of its anti-inflammatory capabilities microalgalbiomass is being considered for applications in tissue engi-neering for the development of scaffolds for use in reconsti-tution of organs and tissues [105 106] This is an importantapplication for humans especially in patients with burnsin which the skin was completely lost [107] Among themost important microalgal compounds with such prop-erties are long-chain polyunsaturated fatty acids (PUFAs)[108 109] sulfurized polysaccharides [110] and pigments[111]
Many microalgal polysaccharides possess the ability tomodulate the immune system through the activation ofmacrophage functions and the induction of reactive oxy-gen species (ROS) nitric oxide (NO) and various othertypes of cytokineschemokines [112] Macrophages are ableto regulate several innate responses and secrete cytokinesand chemocytokines that serve as signals for immune andinflammatory molecular reactions [113] Sulfur polysaccha-rides with anti-inflammatory activity can be applied inskin treatments inhibiting the migration and adhesion ofpolymorphonuclear leukocytes [110] Guzman et al [114]studied the anti-inflammatory capacity of the microalgaChlorella stigmatophora and Phaeodactylum tricomutum andconcluded that bothmicroalgae showed positive responses inthe test of paw edema by carrageenan
The PUFAs especially 1205963 and 1205966 as eicosapentaenoic(EPA) docosahexaenoic (DHA) and arachidonic (AA) acidshave been applied in the treatment of chronic inflammationsuch as rheumatism and skin diseases [108] Ryckebosch etal [115] evaluated the nutritional value of the total lipidsextracted from different PUFAs produced by microalgae Inthis study the microalgae IsochrysisNannochloropsis Phaeo-dactylum Pavlova and Thalassiosira produced 1205963 PUFA asan alternative to fish oil in food
Among the pigments with anti-inflammatory activityfucoxanthin carotenoid found in diatoms [116 117] is capableof stimulating apoptosis in human cancer cells [118] A phy-cocyanin found in cyanobacteria has an anti-inflammatoryactivity that occurs through the inhibition of histaminerelease [111 119]
54 Compounds with Potentiality over Degenerative Dis-eases In humans the oxidation reactions driven by reactiveoxygen species (ROS) can lead to irreversible damage tocellular components including lipids proteins and DNAdegradation andor mutation Consequently this damagecan lead to several syndromes such as cardiovascular dis-ease some cancers and the degenerative diseases of aging[120]
Chronic age-related diseases involve oxidative stress andinflammation and their consequences Chronic inflammationplays a significant role in the mediation of neurodegenerativediseases such as Parkinsonrsquos disease Alzheimerrsquos diseasemultiple sclerosis acquired immunodeficiency syndrome(AIDS) and dementia complex [77]
Natural pigments derived from microalgae (NPs) haveneuroprotective properties being valuable sources as func-tional ingredients in foods and pharmaceutical products thatshow efficient action in the treatment andor prevention ofneurodegenerative diseases Vitamin E has preventive effectsfor many diseases such as atherosclerosis and heart diseaseas well as neurodegenerative diseases such as multiplesclerosis [77]
Carotenoids have great potential benefits to humanhealth including the treatment of degenerative diseases suchas macular degeneration and cataract development Thesecompounds act as antioxidants reducing oxidative damageby ROS Studies indicated that increased intake of phenolsdecreased the occurrence of degenerative diseases Phenoliccompounds from microalgae with the potential to fight freeradicals have been reported [121]
Dunaliella salina is a natural source of 120573-carotene whichproduced a reduced risk of cancer and degenerative diseasesin humans Lutein is effective against various diseases includ-ing cataracts and macular degeneration and in the earlystages of atherosclerosis Extracts of Chlorella sp containing120573-carotene and lutein significantly prevented the cognitivedisability that accompanies Alzheimerrsquos disease in rats It wasalso reported that lutein extracted from Chlorella reducedthe incidence of cancer Likewise carotenoids extractedfrom Chlorella ellipsoidea and Chlorella vulgaris inhibited thegrowth of colon cancer [122] A lycopene extracted fromthe microalgae Chlorella marina significantly reduced theproliferation of prostate cancer inmice [123]This compoundalso reduced total cholesterol and low-density lipoprotein(LDL) levels [123] and improved rheumatoid arthritis [124]
Low plasma levels of lutein have also been associatedwith an increased tendency ofmyocardial infarction whereashigh intake of lutein was related to a decreased risk ofstroke In addition high levels of carotenoids with provi-tamin A activity including 120572-carotene 120573-carotene and 120573-cryptoxanthin have been associated with reduction in therisk of angina pectoris Macular degeneration the lead-ing cause of irreversible vision loss has also been associ-ated with very low consumption of lutein and zeaxanthin[125]
Scientific findings indicate astaxanthin for multimodalintervention formany forms of degenerative diseases includ-ing cardiovascular diseases cancer metabolic syndromecognitive impairment age-related immune dysfunctionstomach and ocular diseases (macular degeneration cataractglaucoma diabetic retinopathy and retinitis pigmentosa)and skin damage [126] High levels of lycopene in plasmaand tissues were inversely related to coronary heart diseasemyocardial infarction and the risk of atherosclerosis [125]
55 Compounds withHealth Promoting Function The impor-tance of microalgae as sources of functional ingredients hasbeen recognized because of their beneficial health effectsNatural pigments are valuable sources of bioactive com-pounds These pigments have various beneficial biologicalactivities such as antioxidant anticancer anti-inflammatoryantiobesity antiangiogenic and neuroprotective action and
10 BioMed Research International
are indicated for the treatment or prevention of severalchronic diseases [77]
The antioxidant potential of carotenoid pigments andtheir ability to prevent cancer aging atherosclerosis coro-nary heart disease and degenerative diseases have beendescribed 120573-Carotene has higher provitamin A activitywhich is essential for vision and the correct functioning ofthe immune system Astaxanthin is linked to many healthbenefits such as protection against lipid peroxidation age-related macular degeneration reduced atherosclerosis andan increased immune response [102]
Fucoxanthin is considered as a promising dietary andweight loss supplement and for the treatment of obesityClinical studies by Abidov et al [127] demonstrated the effectof ldquoxanthigenrdquo a fucoxanthin based antiobesity supplementFurthermore fucoxanthinmay be useful for the prevention ofbone diseases such as osteoporosis and rheumatoid arthritisIt has also been reported to be effective for the therapeutictreatment of diabetic diseases suppressing insulin and hyper-glycemia [77]
Microalgae proteins are of great interest as a source ofbioactive peptides due to their therapeutic potential in thetreatment of various diseases [7] Proteins peptides andamino acids have functions that contribute to health benefitsThese compounds can include growth factors hormones andimmunomodulators and can help to replace damaged tissuesin addition to providing nutritional benefits Microalgaesuch as Chlorella and Spirulina (Arthrospira) may be usedas nutraceuticals or included in functional foods to preventdiseases and damage to cells and tissues due to their richprotein content and amino acid profile [102]
The antimicrobial action of certain enzymes (eglysozyme) and immunoglobulins has been reported andrecommended for people with different diseases (egCrohnrsquos disease) due to the existence of formulations withpeptides and free amino acids Studies of the healtheffects of lysozyme have been reported in the microalgaeSpirulina platensis [128] Chlorella [129] and Dunaliellasalina [130] Spirulina (Arthrospira) and Chlorella biomasspills are marketed as is ldquoHawaiian Spirulina Pacificardquo(httpspirulinagreennutritionalscomau) Other proteinscan also increase the production of cholecystokinin involvedin appetite suppression and the reduction of LDL-cholesterolProtein peptides from Chlorella have a potential as dietarysupplements for the prevention of oxidative stress-relateddiseases such as atherosclerosis coronary heart disease andcancer [39]
The essential fatty acids 120596-3 and 120596-6 in particular areimportant for the integrity of tissues 120574-Linolenic acid hastherapeutic applications in cosmetics to revitalize the skinand thus slow aging Linoleic and linolenic acids are essentialnutrients for the immune system and other related tissueregeneration processes Linoleic acid is also used for thetreatment of hyperplasia of the skin [102]
The most studied microalgal lipid compounds are thepolyunsaturated fatty acids (PUFAs) docosahexaenoic acid(120596-3 C226) (DHA) eicosapentaenoic acid (C20 120596-35)(EPA) and arachidonic acid (120596-6 C204) (ARA) Studies haveshown that dietary120596-3 PUFAs have a protective effect against
atherosclerotic heart disease [131] DHA and EPA showed theability to reduce problems associated with strokes and arthri-tis besides reducing hypertension lipid content (a decreasein triglycerides and an increase of HDL) and acting asanti-inflammatory agents DHA is also important in thedevelopment and function of the nervous system Further-more ARA and EPA are platelet aggregators vasoconstric-tors and vasodilators and have antiaggregative action on theendothelium as well as chemostatic activity in neutrophils[102]
Other lipid compounds with interesting bioactive prop-erties are the microalgal sterols Phytosterols have demon-strated reduction of total cholesterol (LDL) in humans byinhibiting its absorption from the intestine [50] Polysac-charides can be considered as dietary fibers associatedwith different physiological effects Insoluble fiber (cellulosehemicellulose and lignin) mainly promotes the movementof material through the digestive system thereby improvinglaxation and increasing satietyThey can also be considered asprebiotics because they promote the growth of gutmicrofloraincluding probiotic species Soluble fiber (oligosaccharidespectins and 120573-glucans) may reduce cholesterol and regulateblood glucose [7 132]
6 Conclusion
The proven ability of microalgae to produce bioactive com-pounds places these microorganisms in the biotechnologicalspotlight for applications in various areas of study especiallyin the life sciencesThe production ofmicroalgal metaboliteswhich stimulate defense mechanisms in the human bodyhas spurred intense study of the application of microalgalbiomass in various foods and pharmacological and medicalproducts There is obviously a need for further study of theidentified compounds and their activities in the treatmentand prevention of various diseases in addition to an ongoingsearch for other as yet undetected metabolites
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgment
The authors thank the National Counsel of Technologicaland Scientific Development (CNPq) for the Productivityin Technological Development and Innovative ExtensionScholarship
References
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[2] A A El Gamal ldquoBiological importance of marine algaerdquo SaudiPharmaceutical Journal vol 18 no 1 pp 1ndash25 2010
BioMed Research International 11
[3] I Moreno-Garrido ldquoMicroalgae immobilization current tech-niques and usesrdquo Bioresource Technology vol 99 no 10 pp3949ndash3964 2008
[4] R-B Volk and F H Furkert ldquoAntialgal antibacterial andantifungal activity of two metabolites produced and excretedby cyanobacteria during growthrdquoMicrobiological Research vol161 no 2 pp 180ndash186 2006
[5] R-B Volk ldquoA newly developed assay for the quantitativedetermination of antimicrobial (anticyanobacterial) activity ofboth hydrophilic and lipophilic test compounds without anyrestrictionrdquoMicrobiological Research vol 163 no 2 pp 161ndash1672008
[6] D F Smee K W Bailey M-H Wong et al ldquoTreatment ofinfluenza A (H1N1) virus infections in mice and ferrets withcyanovirin-Nrdquo Antiviral Research vol 80 no 3 pp 266ndash2712008
[7] E Ibanez and A Cifuentes ldquoBenefits of using algae as naturalsources of functional ingredientsrdquo Journal of the Science of Foodand Agriculture vol 93 no 4 pp 703ndash709 2013
[8] G Markou and E Nerantzis ldquoMicroalgae for high-valuecompounds and biofuels production a review with focus oncultivation under stress conditionsrdquo Biotechnology Advancesvol 31 no 8 pp 1532ndash1542 2013
[9] R Harun M Singh G M Forde andM K Danquah ldquoBiopro-cess engineering ofmicroalgae to produce a variety of consumerproductsrdquo Renewable and Sustainable Energy Reviews vol 14no 3 pp 1037ndash1047 2010
[10] C Kolympiris N Kalaitzandonakes and D Miller ldquoPublicfunds and local biotechnology firm creationrdquo Research Policyvol 43 no 1 pp 121ndash137 2014
[11] S Bhagavathy P Sumathi and I Jancy Sherene Bell ldquoGreenalgae Chlorococcum humicola-a new source of bioactive com-pounds with antimicrobial activityrdquo Asian Pacific Journal ofTropical Biomedicine vol 1 no 1 pp S1ndashS7 2011
[12] A M F Palavra J P Coelho J G Barroso et al ldquoSupercrit-ical carbon dioxide extraction of bioactive compounds frommicroalgae and volatile oils from aromatic plantsrdquo Journal ofSupercritical Fluids vol 60 pp 21ndash27 2011
[13] I Priyadarshani and B Rath ldquoCommercial and industrialapplications of micro algaemdasha reviewrdquo Journal of Algal BiomassUtilization vol 3 no 4 pp 89ndash100 2012
[14] JW Blunt B R CoppM H GMunro P T Northcote andMR Prinsep ldquoMarine natural productsrdquoNatural Product Reportsvol 23 no 1 pp 26ndash78 2006
[15] A M S Mayer and M T Hamann ldquoMarine pharmacologyin 2001-2002 marine compounds with anthelmintic antibacte-rial anticoagulant antidiabetic antifungal anti-inflammatoryantimalarial antiplatelet antiprotozoal antituberculosis andantiviral activities affecting the cardiovascular immune andnervous systems and other miscellaneous mechanisms ofactionrdquo Comparative Biochemistry and Physiology Part C Toxi-cology amp Pharmacology vol 140 no 3-4 pp 265ndash286 2005
[16] M Plaza S Santoyo L Jaime et al ldquoScreening for bioactivecompounds from algaerdquo Journal of Pharmaceutical and Biomed-ical Analysis vol 51 no 2 pp 450ndash455 2010
[17] I Rodrıguez-Meizoso L Jaime S Santoyo et al ldquoPressurizedfluid extraction of bioactive compounds from Phormidiumspeciesrdquo Journal of Agricultural and Food Chemistry vol 56 no10 pp 3517ndash3523 2008
[18] L R Carvalho A Costa-Neves G A A Conserva et alldquoBiologically active compounds from cyano bacteria extracts in
vivo and in vitro aspectsrdquo Brazilian Journal of Pharmacognosyvol 23 no 3 pp 471ndash480 2013
[19] B Nobre FMarcelo R Passos et al ldquoSupercritical carbon diox-ide extraction of astaxanthin and other carotenoids from themicroalga Haematococcus pluvialisrdquo European Food Researchand Technology vol 223 no 6 pp 787ndash790 2006
[20] R L Mendes A D Reis and A F Palavra ldquoSupercritical CO2
extraction of 120574-linolenic acid and other lipids from Arthrospira(Spirulina)maxima comparison with organic solvent extrac-tionrdquo Food Chemistry vol 99 no 1 pp 57ndash63 2006
[21] I Romano M R Bellitti B Nicolaus et al ldquoLipid profilea useful chemotaxonomic marker for classification of a newcyanobacterium in Spirulina genusrdquo Phytochemistry vol 54 no3 pp 289ndash294 2000
[22] J A C Costa and M G Morais ldquoMicroalgae for food produc-tionrdquo in Fermentation Process Engineering in the Food IndustryC R Soccol A Pandey and C Larroche Eds p 486 Taylor ampFrancis 2013
[23] MAAmbrosi CO Reinehr T E Bertolin et al ldquoPropriedadesde saude de Spirulina spprdquo Revista de Ciencias FarmaceuticasBasica e Aplicada vol 29 no 2 pp 109ndash117 2008
[24] J A Borges G M Rosa L H R Meza A A Henrard M RA Z Souza and J A V Costa ldquoSpirulina sp LEB-18 cultureusing effluent from the anaerobic digestionrdquo Brazilian Journalof Chemical Engineering vol 30 no 2 pp 277ndash287 2013
[25] F S Antelo J A V Costa and S J Kalil ldquoThermal degradationkinetics of the phycocyanin from Spirulina platensisrdquo Biochem-ical Engineering Journal vol 41 no 1 pp 43ndash47 2008
[26] S T Silveira J F M Burkert J A V Costa C A V Burkertand S J Kalil ldquoOptimization of phycocyanin extraction fromSpirulina platensis using factorial designrdquo Bioresource Technol-ogy vol 98 no 8 pp 1629ndash1634 2007
[27] L M Colla C O Reinehr C Reichert and J A V Costa ldquoPro-duction of biomass and nutraceutical compounds by Spirulinaplatensis under different temperature and nitrogen regimesrdquoBioresource Technology vol 98 no 7 pp 1489ndash1493 2007
[28] R P Rastogi and R P Sinha ldquoBiotechnological and industrialsignificance of cyanobacterial secondary metabolitesrdquo Biotech-nology Advances vol 27 no 4 pp 521ndash539 2009
[29] N A E Semary ldquoThe characterisation of bioactive compoundsfrom an Egyptian Leptolyngbya sp strainrdquo Annals of Microbiol-ogy vol 62 no 1 pp 55ndash59 2012
[30] L M Colla A L Muccillo-Baisch and J A Vieira CostaldquoSpirulina platensis effects on the levels of total cholesterol HDLand triacylglycerols in rabbits fed with a hypercholesterolemicdietrdquo Brazilian Archives of Biology and Technology vol 51 no 2pp 405ndash411 2008
[31] P V Torres-Duran A Ferreira-Hermosillo and M A Juarez-Oropeza ldquoAntihyperlipemic and antihypertensive effects ofSpirulina maxima in an open sample of Mexican population apreliminary reportrdquo Lipids in Health and Disease vol 6 article33 2007
[32] S AnshumanMDeepikaG Sharmila andCMuthukumaranldquoEffect of glucose and phytohaemagglutinin (PHA) richPhaseo-lus vulgaris extract on growth and protein synthesis of pharma-ceutically important cyanobacteriaNostoc ellipsosporumNCIM2786rdquo Journal of Genetic Engineering and Biotechnology vol 11no 1 pp 33ndash37 2013
[33] IMaldener andAMMuro-PasterEncyclopedia of Life Sciences(ELS) John Wiley amp Sons Chichester UK 2010
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[34] M Temina H Rezankova T Rezanka and V M DembitskyldquoDiversity of the fatty acids of the Nostoc species and theirstatistical analysisrdquoMicrobiological Research vol 162 no 4 pp308ndash321 2007
[35] Z Deng Q Hu F Lu G Liu and Z Hu ldquoColony developmentand physiological characterization of the edible blue-greenalga Nostoc sphaeroides (Nostocaceae Cyanophyta)rdquo Progressin Natural Science vol 18 no 12 pp 1475ndash1484 2008
[36] M R Boyd K R Gustafson J B McMahon et al ldquoDiscoveryof cyanovirin-N a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycopro-tein gp120 potential applications to microbicide developmentrdquoAntimicrobial Agents and Chemotherapy vol 41 no 7 pp 1521ndash1530 1997
[37] M Wang Y-N Xu G-Z Jiang L-B Li and T-Y KuangldquoMembrane lipids and their fatty acid composition in Nostocflagelliforme cellsrdquoActa Botanica Sinica vol 42 no 12 pp 1263ndash1266 2000
[38] J Masojıdek and O Prasil ldquoThe development of microalgalbiotechnology in the Czech Republicrdquo Journal of IndustrialMicrobiology amp Biotechnology vol 37 no 12 pp 1307ndash1317 2010
[39] M Plaza M Herrero A Alejandro Cifuentes and E IbanezldquoInnovative natural functional ingredients from microalgaerdquoJournal of Agricultural and Food Chemistry vol 57 no 16 pp7159ndash7170 2009
[40] J A V Costa E M Radmann V S Cerqueira G C Santosand M N Calheiros ldquoPerfil de acidos graxos das microalgasChlorella vulgaris e Chlorella minutissima cultivadas em difer-entes condicoesrdquo Alimentos e Nutricao Araraquara vol 17 no4 pp 429ndash436 2006
[41] K H Cha S W Kang C Y Kim B H Um Y R Naand C-H Pan ldquoEffect of pressurized liquids on extraction ofantioxidants from chlorella vulgarisrdquo Journal of Agricultural andFood Chemistry vol 58 no 8 pp 4756ndash4761 2010
[42] F Kokou P Makridis M Kentouri and P Divanach ldquoAntibac-terial activity inmicroalgae culturesrdquoAquaculture Research vol43 no 10 pp 1520ndash1527 2012
[43] L Li W Li Y-H Kim and YW Lee ldquoChlorella vulgaris extractameliorates carbon tetrachloride-induced acute hepatic injuryin micerdquo Experimental and Toxicologic Pathology vol 65 no 1-2 pp 73ndash80 2013
[44] N B Medina-Jaritz L F Carmona-Ugalde J C Lopez-CedilloandF S L Ruiloba-DeLeon ldquoAntibacterial activity ofmethano-lic extracts from Dunaliella salina and Chlorella vulgarisrdquo TheFASEB Journal vol 27 abstract 11675 2013
[45] L Zhao and B V Sweet ldquoLutein and zeaxanthin for maculardegenerationrdquo The American Journal of Health-System Phar-macy vol 65 no 13 pp 1232ndash1238 2008
[46] P Spolaore C Joannis-Cassan E Duran and A IsambertldquoCommercial applications of microalgaerdquo Journal of Bioscienceand Bioengineering vol 101 no 2 pp 87ndash96 2006
[47] C Rosch and C Posten ldquoChallenges and perspectives ofmicroalgae productionrdquo TechnikfolgenabschatzungmdashTheorieund Praxis vol 21 no 1 2012
[48] K Preetha L John C S Subin and K K Vijayan ldquoPhenotypicand genetic characterization of Dunaliella (Chlorophyta) fromIndian salinas and their diversityrdquoAquatic Biosystems vol 8 no1 article 27 2012
[49] A Hosseini Tafreshi and M Shariati ldquoDunaliella biotechnol-ogy methods and applicationsrdquo Journal of Applied Microbiol-ogy vol 107 no 1 pp 14ndash35 2009
[50] M Francavilla P Trotta and R Luque ldquoPhytosterols fromDunaliella tertiolecta and Dunaliella salina a potentially novelindustrial applicationrdquo Bioresource Technology vol 101 no 11pp 4144ndash4150 2010
[51] F F Madkour and M M Abdel-Daim ldquoHepatoprotective andantioxidant activity of dunaliella salina in paracetamol-inducedacute toxicity in ratsrdquo Indian Journal of Pharmaceutical Sciencesvol 75 no 6 pp 642ndash648 2013
[52] T Chang S Ohta N Ikegami H Miyata T Kashimoto andM Kondo ldquoAntibiotic substances produced by a marine greenalgaDunaliella primolectardquo Bioresource Technology vol 44 no2 pp 149ndash153 1993
[53] M Herrero L Jaime P J Martın-Alvarez A Cifuentes and EIbanez ldquoOptimization of the extraction of antioxidants fromDunaliella salina microalga by pressurized liquidsrdquo Journal ofAgricultural and Food Chemistry vol 54 no 15 pp 5597ndash56032006
[54] R Leon M Martın J Vigara C Vilchez and J MVega ldquoMicroalgae mediated photoproduction of 120573-carotene inaqueous-organic two phase systemsrdquo Biomolecular Engineeringvol 20 no 4ndash6 pp 177ndash182 2003
[55] M Garcıa-Gonzalez J Moreno J C Manzano F J Florencioand M G Guerrero ldquoProduction of Dunaliella salina biomassrich in 9-119888119894119904-120573-carotene and lutein in a closed tubular photo-bioreactorrdquo Journal of Biotechnology vol 115 no 1 pp 81ndash902005
[56] D M M Kleinegris M Janssen W A Brandenburg andR H Wijffels ldquoContinuous production of carotenoids fromDunaliella salinardquo Enzyme and Microbial Technology vol 48no 3 pp 253ndash259 2011
[57] P Stolz and B Obermayer ldquoManufacturing microalgae for skincarerdquo Cosmetics amp Toiletries Science Applied vol 120 pp 99ndash106 2005
[58] M N Noaman ldquoEffect of potassium and nitrogen fertilizers onthe growth and biomass of some halophytes grown under highlevels of salinityrdquo Journal of Agronomy vol 3 no 1 pp 25ndash302004
[59] S O Lourenco Cultivo de Microalgas Marinhas Princıpios eAplicacoes RiMa Sao Paulo Brazil 2006
[60] G E Fogg ldquoThe ecological significance of extracellular prod-ucts of phytoplankton photosynthesisrdquo Botanica Marina vol26 no 1 pp 3ndash14 1983
[61] D L Nelson and M M Cox Princıpios de Bioquımica SarvierSao Paulo Brazil 4th edition 2004
[62] T Chrismadha andM A Borowitzka ldquoEffect of cell density andirradiance on growth proximate composition and eicosapen-taenoic acid production of Phaeodactylum tricornutum grownin a tubular photobioreactorrdquo Journal of Applied Phycology vol6 no 1 pp 67ndash74 1994
[63] A C Guedes L A Meireles H M Amaro and F X MalcataldquoChanges in lipid class and fatty acid composition of culturesof Pavlova lutheri in response to light intensityrdquo Journal of theAmerican Oil Chemistsrsquo Society vol 87 no 7 pp 791ndash801 2010
[64] H K Madhyastha S Sivashankari and T M Vatsala ldquoC-phycocyanin from Spirulina fussiformis exposed to blue lightdemonstrates higher efficacy of in vitro antioxidant activityrdquoBiochemical Engineering Journal vol 43 no 2 pp 221ndash2242009
[65] A Vonshak Spirulina platensis (Athrospira) Physiology Cell-Biology and Biotechnoloby Taylor amp Francis London UK 1997
[66] R D Fox Spirulina Production amp Potential Edisud ParisFrance 1996
BioMed Research International 13
[67] C U Ugwu H Aoyagi and H Uchiyama ldquoPhotobioreactorsfor mass cultivation of algaerdquo Bioresource Technology vol 99no 10 pp 4021ndash4028 2008
[68] S V Mohan M V Rohit P Chiranjeevi R Chandra and BNavaneeth ldquoHeterotrophic microalgae cultivation to synergizebiodiesel production with waste remediation progress andperspectivesrdquo Bioresource Technology 2014
[69] M G Morais and J A C Costa ldquoAn open pond system formicroalgal cultivationinrdquo in Biofuels from Algae A Pandey D-J Lee Y Chisti and C R Soccol Eds p 1 Elsevier 2014
[70] R E Lee Phycology Cambridge University Press New YorkNY USA 1980
[71] A RichmondHandbook ofMicroalgalMass Culture CRCPressBoston Mass USA 1990
[72] M Coca V M Barrocal S Lucas G Gonzalez-Benito andM T Garcıa-Cubero ldquoProtein production in Spirulina platensisbiomass using beet vinasse-supplemented culture mediardquo Foodand Bioproducts Processing 2014
[73] P-F Ip and F Chen ldquoPeroxynitrite and nitryl chloride enhanceastaxanthin production by the green microalga Chlorella zofin-giensis in heterotrophic culturerdquo Process Biochemistry vol 40no 11 pp 3595ndash3599 2005
[74] D L Alonso E-H Belarbi J M Fernandez-Sevilla JRodrıguez-Ruiz and E M Grima ldquoAcyl lipid compositionvariation related to culture age and nitrogen concentration incontinuous culture of the microalga Phaeodactylum tricornu-tumrdquo Phytochemistry vol 54 no 5 pp 461ndash471 2000
[75] W Schmidell A U Lima E Aquarone and W BorzaniBiotecnologia Industrial Volume 2 Edgard Blucher Sao PauloBrazil 2001
[76] R R L Guillard ldquoCulture of phytoplankton for feeding marineinvertebratesrdquo in Culture of Marine Invertebrate Animals W LSmith and M H Chanley Eds pp 29ndash60 Plenum New YorkNY USA 1975
[77] R Pangestuti and S-K Kim ldquoBiological activities and healthbenefit effects of natural pigments derived from marine algaerdquoJournal of Functional Foods vol 3 no 4 pp 255ndash266 2011
[78] K Skjanes C Rebours and P Lindblad ldquoPotential for greenmicroalgae to produce hydrogen pharmaceuticals and otherhigh value products in a combined processrdquo Critical Reviews inBiotechnology vol 33 no 2 pp 172ndash215 2013
[79] I Rodrıguez-Meizoso L Jaime S Santoyo F J Senorans ACifuentes and E Ibanez ldquoSubcritical water extraction andcharacterization of bioactive compounds from Haematococcuspluvialis microalgardquo Journal of Pharmaceutical and BiomedicalAnalysis vol 51 no 2 pp 456ndash463 2010
[80] M Herrero M Castro-Puyana J A Mendiola and E IbanezldquoCompressed fluids for the extraction of bioactive compoundsrdquoTrends in Analytical Chemistry vol 43 pp 67ndash83 2013
[81] N K Singh and D W Dhar ldquoMicroalgae as second generationbiofuel A reviewrdquo Agronomy for Sustainable Development vol31 no 4 pp 605ndash629 2011
[82] L Brennan and P Owende ldquoBiofuels frommicroalgae towardsmeeting advanced fuel standardsrdquo in Advanced Biofuels andBioproducts JW Lee Ed pp 553ndash599 Springer NewYork NYUSA 2013
[83] A Singh P S Nigam and J D Murphy ldquoRenewable fuels fromalgae an answer to debatable land based fuelsrdquo BioresourceTechnology vol 102 no 1 pp 10ndash16 2011
[84] P Perez-Lopez S Gonzalez-Garcıa R G Ulloa J SineiroG Feijoo and M T Moreira ldquoLife cycle assessment of the
production of bioactive compounds from Tetraselmis suecica atpilot scalerdquo Journal of Cleaner Production vol 64 pp 323ndash3312014
[85] B Subhadra ldquoAlgal biorefinery-based industry an approachto address fuel and food insecurity for a carbon-smart worldrdquoJournal of the Science of Food and Agriculture vol 91 no 1 pp2ndash13 2011
[86] D J Newman and G M Cragg ldquoNatural products as sourcesof new drugs over the 30 years from 1981 to 2010rdquo Journal ofNatural Products vol 75 no 3 pp 311ndash335 2012
[87] H-B Li K-W Cheng C-C Wong K-W Fan F Chen andY Jiang ldquoEvaluation of antioxidant capacity and total phenoliccontent of different fractions of selected microalgaerdquo FoodChemistry vol 102 no 3 pp 771ndash776 2007
[88] T M Mata A A Martins and N S Caetano ldquoMicroalgaefor biodiesel production and other applications a reviewrdquoRenewable and Sustainable EnergyReviews vol 14 no 1 pp 217ndash232 2010
[89] A Gupta and J K Sainis ldquoIsolation of C-phycocyanin fromSynechococcus sp (Anacystis nidulans BD1)rdquo Journal of AppliedPhycology vol 22 no 3 pp 231ndash233 2010
[90] P J Viskari and C L Colyer ldquoRapid extraction of phyco-biliproteins from cultured cyanobacteria samplesrdquo AnalyticalBiochemistry vol 319 no 2 pp 263ndash271 2003
[91] R Bermejo Roman J M Alvarez-Pez F G Acien Fernandezand E Molina Grima ldquoRecovery of pure B-phycoerythrin fromthe microalga Porphyridium cruentumrdquo Journal of Biotechnol-ogy vol 93 no 1 pp 73ndash85 2002
[92] C I Cazzonelli ldquoCarotenoids in nature insights from plantsand beyondrdquo Functional Plant Biology vol 38 no 11 pp 833ndash847 2011
[93] M A Hejazi and R HWijffels ldquoMilking of microalgaerdquo Trendsin Biotechnology vol 22 no 4 pp 189ndash194 2004
[94] S Arad and O Levy-Ontman ldquoRed microalgal cell-wallpolysaccharides biotechnological aspectsrdquo Current Opinion inBiotechnology vol 21 no 3 pp 358ndash364 2010
[95] M Kim J H Yim S-Y Kim et al ldquoIn vitro inhibitionof influenza A virus infection by marine microalga-derivedsulfated polysaccharide p-KG03rdquoAntiviral Research vol 93 no2 pp 253ndash259 2012
[96] Z A Mohamed ldquoPolysaccharides as a protective responseagainst microcystin-induced oxidative stress in Chlorella vul-garis and Scenedesmus quadricauda and their possible signifi-cance in the aquatic ecosystemrdquo Ecotoxicology vol 17 no 6 pp504ndash516 2008
[97] T Tannin-Spitz M Bergman D Van-Moppes S Grossmanand S Arad ldquoAntioxidant activity of the polysaccharide of thered microalga Porphyridium sprdquo Journal of Applied Phycologyvol 17 no 3 pp 215ndash222 2005
[98] J W Prakash M Johnson and S Jeeva ldquoAntimicrobial activityof certain fresh water microalgae from Thamirabarani RiverTamil Nadu South Indiardquo Asian Pacific Journal of TropicalBiomedicine vol 1 supplement no 2 pp S170ndashS173 2011
[99] H M Amaro A C Guedes and F X Malcata ldquoAntimicrobialactivities of microalgae an invited reviewrdquo in Science againstMicrobial Pathogens Communicating Current Research andTechnological Advances A Mendez-Vilas Ed pp 1272ndash12802011
[100] V J Smith A PDesbois and E ADyrynda ldquoConventional andunconventional antimicrobials from fish marine invertebratesand micro-algaerdquo Marine Drugs vol 8 no 4 pp 1213ndash12622010
14 BioMed Research International
[101] M F D J Raposo A M M B de Morais and R M SC de Morais ldquoInfluence of sulphate on the composition andantibacterial and antiviral properties of the exopolysaccharidefrom Porphyridium cruentumrdquo Life Sciences vol 101 no 1-2 pp56ndash63 2014
[102] M F De Jesus Raposo R M S C De Morais and A M M BDe Morais ldquoHealth applications of bioactive compounds frommarine microalgaerdquo Life Sciences vol 93 no 15 pp 479ndash4862013
[103] A Smelcerovic Z Knezevic-Jugovic and Z PetronijevicldquoMicrobial polysaccharides and their derivatives as current andprospective pharmaceuticalsrdquo Current Pharmaceutical Designvol 14 no 29 pp 3168ndash3195 2008
[104] M T Madigan J M Martinko P V Dunlap and D P ClarkMicrobiologia de Brock Artmed Editora 12th edition 2010
[105] M G de Morais J A V Costa P H L Pranke et alldquoDevelopment of a newnanofiber scaffold for usewith stemcellsin a third degree burn animal modelrdquo Burns Oxford vol 40 no8 pp 1650ndash1660 2014
[106] M G de Morais C Stillings R Dersch et al ldquoPreparation ofnanofibers containing the microalga Spirulina (Arthrospira)rdquoBioresource Technology vol 101 no 8 pp 2872ndash2876 2010
[107] D Steffens M Lersch A Rosa et al ldquoA new biomaterialof nanofibers with the microalga Spirulina as scaffolds tocultivate with stem cells for use in tissue engineeringrdquo Journalof Biomedical Nanotechnology vol 9 no 4 pp 710ndash718 2013
[108] C Barrow and F ShahidiMarine Nutraceuticals and FunctionalFoods CRC Press Taylor amp Francis Boca Raton Fla USA2008
[109] M N A Khan J-Y ChoM-C Lee et al ldquoIsolation of two anti-inflammatory and one pro-inflammatory polyunsaturated fattyacids from the brown seaweed Undaria pinnatifidardquo Journal ofAgricultural and Food Chemistry vol 55 no 17 pp 6984ndash69882007
[110] M S Matsui N Muizzuddin S Arad and K MarenusldquoSulfated polysaccharides from redmicroalgae have antiinflam-matory properties in vitro and in vivordquo Applied Biochemistryand Biotechnology vol 104 no 1 pp 13ndash22 2003
[111] V B Bhat and K M Madyastha ldquoScavenging of peroxynitriteby phycocyanin and phycocyanobilin from Spirulina platensisprotection against oxidative damage to DNArdquo Biochemical andBiophysical Research Communications vol 285 no 2 pp 262ndash266 2001
[112] I A Schepetkin and M T Quinn ldquoBotanical polysaccharidesmacrophage immunomodulation and therapeutic potentialrdquoInternational Immunopharmacology vol 6 no 3 pp 317ndash3332006
[113] J K Park Z-H Kim C G Lee et al ldquoCharacterization andimmunostimulating activity of a water-soluble polysaccharideisolated from Haematococcus lacustrisrdquo Biotechnology and Bio-process Engineering vol 16 no 6 pp 1090ndash1098 2011
[114] S Guzman A Gato M Lamela M Freire-Garabal and J MCalleja ldquoAnti-inflammatory and immunomodulatory activitiesof polysaccharide from Chlorella stigmatophora and Phaeo-dactylum tricornutumrdquo Phytotherapy Research vol 17 no 6 pp665ndash670 2003
[115] E Ryckebosch C Bruneel R Termote-Verhalle K Goiris KMuylaert and I Foubert ldquoNutritional evaluation of microalgaeoils rich in omega-3 long chain polyunsaturated fatty acids as analternative for fish oilrdquo Food Chemistry vol 160 pp 393ndash4002014
[116] P Zhao Z Zang X Xie A Huang and G Wang ldquoTheinfluence of different flocculants on the physiological activityand fucoxanthin production of Phaeodactylum tricornutumrdquoProcess Biochemistry vol 49 no 4 pp 681ndash687 2014
[117] D Moreau C Tomasoni C Jacquot et al ldquoCultivated microal-gae and the carotenoid fucoxanthin from Odontella auritaas potent anti-proliferative agents in bronchopulmonary andepithelial cell linesrdquo Environmental Toxicology and Pharmacol-ogy vol 22 no 1 pp 97ndash103 2006
[118] H Maeda M Hosokawa T Sashima K Funayama and KMiyashita ldquoFucoxanthin from edible seaweed Undaria pinnati-fida shows antiobesity effect through UCP1 expression in whiteadipose tissuesrdquo Biochemical and Biophysical Research Commu-nications vol 332 no 2 pp 392ndash397 2005
[119] J E Piero Estrada P Bermejo Bescos and A M Villar delFresno ldquoAntioxidant activity of different fractions of Spirulinaplatensis protean extractrdquo IL Farmaco vol 56 no 5ndash7 pp 497ndash500 2001
[120] S-M Kang S-J Heo K-N Kim S-H Lee and Y-JJeon ldquoIsolation and identification of new compound 2710158401015840-phloroglucinol-661015840-bieckol from brown algae Ecklonia cavaand its antioxidant effectrdquo Journal of Functional Foods vol 4no 1 pp 158ndash166 2012
[121] HHAbdEl-Baky F K El Baz andG S El-Baroty ldquoProductionof phenolic compounds from Spirulinamaximamicroalgae andits protective effectsrdquoAfrican Journal of Biotechnology vol 8 no24 pp 7059ndash7067 2009
[122] A C Guedes H M Amaro and F X Malcata ldquoMicroalgae assources of carotenoidsrdquoMarineDrugs vol 9 no 4 pp 625ndash6442011
[123] G L Renju G M Kurup and K C H Saritha ldquoEffect oflycopene from Chlorella marina on high cholesterol-inducedoxidative damage and inflammation in ratsrdquo Inflammopharma-cology vol 22 no 1 pp 45ndash54 2014
[124] G L Renju G M Kurup and C H S Kumari ldquoAnti-inflammatory activity of lycopene isolated from Chlorellamarina onType II Collagen induced arthritis in SpragueDawleyratsrdquo Immunopharmacology and Immunotoxicology vol 35 no2 pp 282ndash291 2013
[125] C Vılchez E Forjan M Cuaresma F Bedmar I Garbayo andJ M Vega ldquoMarine carotenoids biological functions andcommercial applicationsrdquo Marine Drugs vol 9 no 3 pp 319ndash333 2011
[126] G Richardson ldquoBeyond eye healthrdquo Life Extension Magazine2011 httpwwwleforgMagazine20117Beyond-Eye-HealthPage-01
[127] M Abidov Z Ramazanov R Seifulla and S Grachev ldquoTheeffects of Xanthigen in the weight management of obesepremenopausal women with non-alcoholic fatty liver diseaseand normal liver fatrdquo Diabetes Obesity and Metabolism vol 12no 1 pp 72ndash81 2010
[128] H M Ragap R H Khalil and H HMutawie ldquoImmunostimu-lant effects of dietary Spirulina platensis on tilapia Oreochromisniloticusrdquo Journal of Applied Pharmaceutical Science vol 2 no2 pp 26ndash31 2012
[129] W Xu Z Gao Z Qi M Qiu J-Q Peng and R Shao ldquoEffect ofdietary chlorella on the growth performance and physiologicalparameters of gibel carp Carassius auratus gibeliordquo TurkishJournal of Fisheries and Aquatic Sciences vol 14 no 1 pp 53ndash572014
[130] P Amaninejad H Emadi M Ematiazjoo et al ldquoEffects ofDunaliella microalgae (Dunaliella salina) on different level of
BioMed Research International 15
IgM Immunoglobulin in rainbow trout (Oncrohynchusmykiss)rdquoGlobal Journal of Biodiversity Science and Management vol 3no 2 pp 237ndash242 2013
[131] V Mimouni L Ulmann V Pasquet et al ldquoThe potential ofmicroalgae for the production of bioactive molecules of phar-maceutical interestrdquoCurrent Pharmaceutical Biotechnology vol13 no 15 pp 2733ndash2750 2012
[132] S M Tosh and S Yada ldquoDietary fibres in pulse seeds and frac-tions characterization functional attributes and applicationsrdquoFood Research International vol 43 no 2 pp 450ndash460 2010
[133] H M Amaro R Barros A C Guedes I Sousa-Pinto and FXMalcata ldquoMicroalgal compoundsmodulate carcinogenesis inthe gastrointestinal tractrdquo Trends in Biotechnology vol 31 no 2pp 92ndash98 2013
[134] S S M Mostafa ldquoMicroalgal biotechnology prospects andapplicationsrdquo in Plant Science chapter 12 pp 275ndash314 InTech2012
[135] L Custodio T Justo L Silvestre et al ldquoMicroalgae of dif-ferent phyla display antioxidant metal chelating and acetyl-cholinesterase inhibitory activitiesrdquoFoodChemistry vol 131 no1 pp 134ndash140 2012
[136] C-CHu J-T Lin F-J Lu F-P Chou andD-J Yang ldquoDetermi-nation of carotenoids in Dunaliella salina cultivated in Taiwanand antioxidant capacity of the algal carotenoid extractrdquo FoodChemistry vol 109 no 2 pp 439ndash446 2008
Microalgal biomass is considered a rich natural source ofantioxidants with potential applications in food cosmet-ics and medicine [87] Antioxidant compounds such asdimethylsulfoniopropionate and mycosporine amino acidswere isolated frommicroalgae and are potent chemical block-ers ofUV radiation [88] In addition to these compounds pig-ments lipids and polysaccharides with antioxidant activitycan also be found in microalgal biomass
Carotenoids and phycocyanins are the pigments mostused in scientific research C-phycocyanin (C-PC) is a bluephotosynthetic pigment that belongs to the group of phyco-biliproteins found in large quantities in the cyanobacteriaRhodophyta and Cryptophyte [89] Phycocyanin has appli-cations as a nutrient and natural food colorants and cosmet-ics It is usually extracted from the biomass of Spirulina [90]and Porphyridium cruentum [91] and Synechococcus [89]
Among the carotenoid compounds 120573-carotene andastaxanthin are prominent These compounds have appli-cation in the food and pharmaceutical industries becauseof their antioxidant properties and pigmentation ability Inmicroalgal metabolism they protect photosynthetic tissuesagainst damage caused by light and oxygen [92] Dunaliellasalina is a microalga recognized as a major biological sourceof 120573-carotene pigment producing more than 14 in drybiomass [46] H pluvialis is a source of the pigment astax-anthin producing 1ndash8 of astaxanthin as dry biomass [93]
Polysaccharides represent a class of high value-addedcomponents with applications in food cosmetics fabrics sta-bilizers emulsifiers and medicine [94] Microalgal polysac-charides contain sulphate esters are referred to as sulfatedpolysaccharides and possess unique medical applicationsThe basic mechanism of therapeutic action is based on thestimulation of macrophages and modulation The biologicalactivity of sulfur polysaccharides is linked to their sugarcomposition position and degree of sulfation [95] Amongthe microalgae capable of producing these compounds areChlorella vulgaris Scenedesmus quadricauda [96] and Por-phyridium sp [97]
52 Compounds with Antimicrobial Activity The importanceof discovering new compounds with antimicrobial activityis driven by the development of antibiotic resistance inhumans due to constant clinical use of antibioticsMicroalgaeare an important source of antibiotics with a broad andefficient antibacterial activity [11] The antimicrobial activityof these microorganisms is due to the ability to synthesizecompounds such as fatty acids acrylic acids halogenatedaliphatic compounds terpenoids sterols sulfur-containingheterocyclic compounds carbohydrates acetogenins andphenols [98]
The antimicrobial activity of extracts from microalgae isrelated to its lipid composition The antimicrobial action ofmicroalgae is also noteworthy because of the potential toproduce compounds such as 120572- and 120573-ionone 120573-cyclocitralneophytadiene and phytol [99] Microalgae antimicrobialactivity against human pathogens such as Escherichia coliPseudomonas aeruginosa Staphylococcus aureus and Staphy-lococcus epidermidis has been attributed to 120574-linolenic acid
The mechanism of action of fatty acids affects variousstructures in microorganisms however cell membranes arethe most impacted Membrane damage most likely leadsto a loss of internal substances from the cells and theentry of harmful components reduces nutrient absorption inaddition to inhibiting cellular respiration The ability of fattyacids to interfere with bacterial growth depends on boththeir chain length and the degree of unsaturation Fatty acidswith more than 10 carbon atoms apparently induce lysis ofbacterial protoplasts [99]
Microbial polysaccharides and other biological com-pounds have antiviral and antimicrobial action Microalgaeproduce extracellular sulfated polysaccharide (EPS) withacidic characteristics that has a potential as a therapeuticagent [101] Highly sulfated antiviral polysaccharides fromseveral species of microalgae consist mainly of xylose glu-cose and galactose The EPS sulfate groups determine somecharacteristics of polysaccharides it has been found thathigher sulphate contents induced higher antiviral activities[94 101] The inhibitory effect of polysaccharides of microal-gal origin is due to viral interactions or positive charges onthe cell surface thereby preventing penetration of the virusinto host cells [99]
The cyanobacterium Spirulina (Arthrospira) can producesulfated polysaccharides that have already found applicationsas antiviral agents both in vivo and in vitro [102] Eukaryoticmicroalgae such as Chlorella sp and Dunaliella sp produceand secrete polysaccharides at relatively high levels [17] Theantibacterial ability of Spirulina has been correlated withtheir volatile composition resulting in the identification of15 elements which constitutes 96 of total compounds Themajor volatile components produced by Spirulina consist ofheptadecane (40) and tetradecane (35) [39]
Some studies have reported that sulfated polysaccharidesderived from microalgae inhibit viral infection such asencephalomyocarditis virus Herpes simplex virus types 1and 2 (HSV1 HSV2) human immunodeficiency virus (HIV)hemorrhagic septicemia in salmonid virus swine fever virusand varicella virus [99 103] Carrageenan is a sulfatedpolysaccharide that can directly bind to human papillo-mavirus to inhibit not only the viral adsorption process butalso the input and subsequent process of the uncoating of thevirus [101]
53 Compounds with Anti-Inflammatory Action Inflam-mation is an immediate reaction to a cell or tissueinjury caused by noxious stimuli such as toxins andpathogens In this situation the body recognizes theagents responsible for the attack and attempts to neu-tralize them as quickly as possible Inflammation causesredness swelling heat and pain usually located at thesite of infection [104] Ingestion of anti-inflammatory com-pounds enhances the bodyrsquos immune response and helpsto prevent disease and aids the healing process Microal-gae produce several anti-inflammatory compounds in their
BioMed Research International 9
biomass that may exert a protective function in the bodywhen consumed as food or used as pharmaceuticals andcosmetics
Because of its anti-inflammatory capabilities microalgalbiomass is being considered for applications in tissue engi-neering for the development of scaffolds for use in reconsti-tution of organs and tissues [105 106] This is an importantapplication for humans especially in patients with burnsin which the skin was completely lost [107] Among themost important microalgal compounds with such prop-erties are long-chain polyunsaturated fatty acids (PUFAs)[108 109] sulfurized polysaccharides [110] and pigments[111]
Many microalgal polysaccharides possess the ability tomodulate the immune system through the activation ofmacrophage functions and the induction of reactive oxy-gen species (ROS) nitric oxide (NO) and various othertypes of cytokineschemokines [112] Macrophages are ableto regulate several innate responses and secrete cytokinesand chemocytokines that serve as signals for immune andinflammatory molecular reactions [113] Sulfur polysaccha-rides with anti-inflammatory activity can be applied inskin treatments inhibiting the migration and adhesion ofpolymorphonuclear leukocytes [110] Guzman et al [114]studied the anti-inflammatory capacity of the microalgaChlorella stigmatophora and Phaeodactylum tricomutum andconcluded that bothmicroalgae showed positive responses inthe test of paw edema by carrageenan
The PUFAs especially 1205963 and 1205966 as eicosapentaenoic(EPA) docosahexaenoic (DHA) and arachidonic (AA) acidshave been applied in the treatment of chronic inflammationsuch as rheumatism and skin diseases [108] Ryckebosch etal [115] evaluated the nutritional value of the total lipidsextracted from different PUFAs produced by microalgae Inthis study the microalgae IsochrysisNannochloropsis Phaeo-dactylum Pavlova and Thalassiosira produced 1205963 PUFA asan alternative to fish oil in food
Among the pigments with anti-inflammatory activityfucoxanthin carotenoid found in diatoms [116 117] is capableof stimulating apoptosis in human cancer cells [118] A phy-cocyanin found in cyanobacteria has an anti-inflammatoryactivity that occurs through the inhibition of histaminerelease [111 119]
54 Compounds with Potentiality over Degenerative Dis-eases In humans the oxidation reactions driven by reactiveoxygen species (ROS) can lead to irreversible damage tocellular components including lipids proteins and DNAdegradation andor mutation Consequently this damagecan lead to several syndromes such as cardiovascular dis-ease some cancers and the degenerative diseases of aging[120]
Chronic age-related diseases involve oxidative stress andinflammation and their consequences Chronic inflammationplays a significant role in the mediation of neurodegenerativediseases such as Parkinsonrsquos disease Alzheimerrsquos diseasemultiple sclerosis acquired immunodeficiency syndrome(AIDS) and dementia complex [77]
Natural pigments derived from microalgae (NPs) haveneuroprotective properties being valuable sources as func-tional ingredients in foods and pharmaceutical products thatshow efficient action in the treatment andor prevention ofneurodegenerative diseases Vitamin E has preventive effectsfor many diseases such as atherosclerosis and heart diseaseas well as neurodegenerative diseases such as multiplesclerosis [77]
Carotenoids have great potential benefits to humanhealth including the treatment of degenerative diseases suchas macular degeneration and cataract development Thesecompounds act as antioxidants reducing oxidative damageby ROS Studies indicated that increased intake of phenolsdecreased the occurrence of degenerative diseases Phenoliccompounds from microalgae with the potential to fight freeradicals have been reported [121]
Dunaliella salina is a natural source of 120573-carotene whichproduced a reduced risk of cancer and degenerative diseasesin humans Lutein is effective against various diseases includ-ing cataracts and macular degeneration and in the earlystages of atherosclerosis Extracts of Chlorella sp containing120573-carotene and lutein significantly prevented the cognitivedisability that accompanies Alzheimerrsquos disease in rats It wasalso reported that lutein extracted from Chlorella reducedthe incidence of cancer Likewise carotenoids extractedfrom Chlorella ellipsoidea and Chlorella vulgaris inhibited thegrowth of colon cancer [122] A lycopene extracted fromthe microalgae Chlorella marina significantly reduced theproliferation of prostate cancer inmice [123]This compoundalso reduced total cholesterol and low-density lipoprotein(LDL) levels [123] and improved rheumatoid arthritis [124]
Low plasma levels of lutein have also been associatedwith an increased tendency ofmyocardial infarction whereashigh intake of lutein was related to a decreased risk ofstroke In addition high levels of carotenoids with provi-tamin A activity including 120572-carotene 120573-carotene and 120573-cryptoxanthin have been associated with reduction in therisk of angina pectoris Macular degeneration the lead-ing cause of irreversible vision loss has also been associ-ated with very low consumption of lutein and zeaxanthin[125]
Scientific findings indicate astaxanthin for multimodalintervention formany forms of degenerative diseases includ-ing cardiovascular diseases cancer metabolic syndromecognitive impairment age-related immune dysfunctionstomach and ocular diseases (macular degeneration cataractglaucoma diabetic retinopathy and retinitis pigmentosa)and skin damage [126] High levels of lycopene in plasmaand tissues were inversely related to coronary heart diseasemyocardial infarction and the risk of atherosclerosis [125]
55 Compounds withHealth Promoting Function The impor-tance of microalgae as sources of functional ingredients hasbeen recognized because of their beneficial health effectsNatural pigments are valuable sources of bioactive com-pounds These pigments have various beneficial biologicalactivities such as antioxidant anticancer anti-inflammatoryantiobesity antiangiogenic and neuroprotective action and
10 BioMed Research International
are indicated for the treatment or prevention of severalchronic diseases [77]
The antioxidant potential of carotenoid pigments andtheir ability to prevent cancer aging atherosclerosis coro-nary heart disease and degenerative diseases have beendescribed 120573-Carotene has higher provitamin A activitywhich is essential for vision and the correct functioning ofthe immune system Astaxanthin is linked to many healthbenefits such as protection against lipid peroxidation age-related macular degeneration reduced atherosclerosis andan increased immune response [102]
Fucoxanthin is considered as a promising dietary andweight loss supplement and for the treatment of obesityClinical studies by Abidov et al [127] demonstrated the effectof ldquoxanthigenrdquo a fucoxanthin based antiobesity supplementFurthermore fucoxanthinmay be useful for the prevention ofbone diseases such as osteoporosis and rheumatoid arthritisIt has also been reported to be effective for the therapeutictreatment of diabetic diseases suppressing insulin and hyper-glycemia [77]
Microalgae proteins are of great interest as a source ofbioactive peptides due to their therapeutic potential in thetreatment of various diseases [7] Proteins peptides andamino acids have functions that contribute to health benefitsThese compounds can include growth factors hormones andimmunomodulators and can help to replace damaged tissuesin addition to providing nutritional benefits Microalgaesuch as Chlorella and Spirulina (Arthrospira) may be usedas nutraceuticals or included in functional foods to preventdiseases and damage to cells and tissues due to their richprotein content and amino acid profile [102]
The antimicrobial action of certain enzymes (eglysozyme) and immunoglobulins has been reported andrecommended for people with different diseases (egCrohnrsquos disease) due to the existence of formulations withpeptides and free amino acids Studies of the healtheffects of lysozyme have been reported in the microalgaeSpirulina platensis [128] Chlorella [129] and Dunaliellasalina [130] Spirulina (Arthrospira) and Chlorella biomasspills are marketed as is ldquoHawaiian Spirulina Pacificardquo(httpspirulinagreennutritionalscomau) Other proteinscan also increase the production of cholecystokinin involvedin appetite suppression and the reduction of LDL-cholesterolProtein peptides from Chlorella have a potential as dietarysupplements for the prevention of oxidative stress-relateddiseases such as atherosclerosis coronary heart disease andcancer [39]
The essential fatty acids 120596-3 and 120596-6 in particular areimportant for the integrity of tissues 120574-Linolenic acid hastherapeutic applications in cosmetics to revitalize the skinand thus slow aging Linoleic and linolenic acids are essentialnutrients for the immune system and other related tissueregeneration processes Linoleic acid is also used for thetreatment of hyperplasia of the skin [102]
The most studied microalgal lipid compounds are thepolyunsaturated fatty acids (PUFAs) docosahexaenoic acid(120596-3 C226) (DHA) eicosapentaenoic acid (C20 120596-35)(EPA) and arachidonic acid (120596-6 C204) (ARA) Studies haveshown that dietary120596-3 PUFAs have a protective effect against
atherosclerotic heart disease [131] DHA and EPA showed theability to reduce problems associated with strokes and arthri-tis besides reducing hypertension lipid content (a decreasein triglycerides and an increase of HDL) and acting asanti-inflammatory agents DHA is also important in thedevelopment and function of the nervous system Further-more ARA and EPA are platelet aggregators vasoconstric-tors and vasodilators and have antiaggregative action on theendothelium as well as chemostatic activity in neutrophils[102]
Other lipid compounds with interesting bioactive prop-erties are the microalgal sterols Phytosterols have demon-strated reduction of total cholesterol (LDL) in humans byinhibiting its absorption from the intestine [50] Polysac-charides can be considered as dietary fibers associatedwith different physiological effects Insoluble fiber (cellulosehemicellulose and lignin) mainly promotes the movementof material through the digestive system thereby improvinglaxation and increasing satietyThey can also be considered asprebiotics because they promote the growth of gutmicrofloraincluding probiotic species Soluble fiber (oligosaccharidespectins and 120573-glucans) may reduce cholesterol and regulateblood glucose [7 132]
6 Conclusion
The proven ability of microalgae to produce bioactive com-pounds places these microorganisms in the biotechnologicalspotlight for applications in various areas of study especiallyin the life sciencesThe production ofmicroalgal metaboliteswhich stimulate defense mechanisms in the human bodyhas spurred intense study of the application of microalgalbiomass in various foods and pharmacological and medicalproducts There is obviously a need for further study of theidentified compounds and their activities in the treatmentand prevention of various diseases in addition to an ongoingsearch for other as yet undetected metabolites
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgment
The authors thank the National Counsel of Technologicaland Scientific Development (CNPq) for the Productivityin Technological Development and Innovative ExtensionScholarship
References
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[2] A A El Gamal ldquoBiological importance of marine algaerdquo SaudiPharmaceutical Journal vol 18 no 1 pp 1ndash25 2010
BioMed Research International 11
[3] I Moreno-Garrido ldquoMicroalgae immobilization current tech-niques and usesrdquo Bioresource Technology vol 99 no 10 pp3949ndash3964 2008
[4] R-B Volk and F H Furkert ldquoAntialgal antibacterial andantifungal activity of two metabolites produced and excretedby cyanobacteria during growthrdquoMicrobiological Research vol161 no 2 pp 180ndash186 2006
[5] R-B Volk ldquoA newly developed assay for the quantitativedetermination of antimicrobial (anticyanobacterial) activity ofboth hydrophilic and lipophilic test compounds without anyrestrictionrdquoMicrobiological Research vol 163 no 2 pp 161ndash1672008
[6] D F Smee K W Bailey M-H Wong et al ldquoTreatment ofinfluenza A (H1N1) virus infections in mice and ferrets withcyanovirin-Nrdquo Antiviral Research vol 80 no 3 pp 266ndash2712008
[7] E Ibanez and A Cifuentes ldquoBenefits of using algae as naturalsources of functional ingredientsrdquo Journal of the Science of Foodand Agriculture vol 93 no 4 pp 703ndash709 2013
[8] G Markou and E Nerantzis ldquoMicroalgae for high-valuecompounds and biofuels production a review with focus oncultivation under stress conditionsrdquo Biotechnology Advancesvol 31 no 8 pp 1532ndash1542 2013
[9] R Harun M Singh G M Forde andM K Danquah ldquoBiopro-cess engineering ofmicroalgae to produce a variety of consumerproductsrdquo Renewable and Sustainable Energy Reviews vol 14no 3 pp 1037ndash1047 2010
[10] C Kolympiris N Kalaitzandonakes and D Miller ldquoPublicfunds and local biotechnology firm creationrdquo Research Policyvol 43 no 1 pp 121ndash137 2014
[11] S Bhagavathy P Sumathi and I Jancy Sherene Bell ldquoGreenalgae Chlorococcum humicola-a new source of bioactive com-pounds with antimicrobial activityrdquo Asian Pacific Journal ofTropical Biomedicine vol 1 no 1 pp S1ndashS7 2011
[12] A M F Palavra J P Coelho J G Barroso et al ldquoSupercrit-ical carbon dioxide extraction of bioactive compounds frommicroalgae and volatile oils from aromatic plantsrdquo Journal ofSupercritical Fluids vol 60 pp 21ndash27 2011
[13] I Priyadarshani and B Rath ldquoCommercial and industrialapplications of micro algaemdasha reviewrdquo Journal of Algal BiomassUtilization vol 3 no 4 pp 89ndash100 2012
[14] JW Blunt B R CoppM H GMunro P T Northcote andMR Prinsep ldquoMarine natural productsrdquoNatural Product Reportsvol 23 no 1 pp 26ndash78 2006
[15] A M S Mayer and M T Hamann ldquoMarine pharmacologyin 2001-2002 marine compounds with anthelmintic antibacte-rial anticoagulant antidiabetic antifungal anti-inflammatoryantimalarial antiplatelet antiprotozoal antituberculosis andantiviral activities affecting the cardiovascular immune andnervous systems and other miscellaneous mechanisms ofactionrdquo Comparative Biochemistry and Physiology Part C Toxi-cology amp Pharmacology vol 140 no 3-4 pp 265ndash286 2005
[16] M Plaza S Santoyo L Jaime et al ldquoScreening for bioactivecompounds from algaerdquo Journal of Pharmaceutical and Biomed-ical Analysis vol 51 no 2 pp 450ndash455 2010
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vivo and in vitro aspectsrdquo Brazilian Journal of Pharmacognosyvol 23 no 3 pp 471ndash480 2013
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extraction of 120574-linolenic acid and other lipids from Arthrospira(Spirulina)maxima comparison with organic solvent extrac-tionrdquo Food Chemistry vol 99 no 1 pp 57ndash63 2006
[21] I Romano M R Bellitti B Nicolaus et al ldquoLipid profilea useful chemotaxonomic marker for classification of a newcyanobacterium in Spirulina genusrdquo Phytochemistry vol 54 no3 pp 289ndash294 2000
[22] J A C Costa and M G Morais ldquoMicroalgae for food produc-tionrdquo in Fermentation Process Engineering in the Food IndustryC R Soccol A Pandey and C Larroche Eds p 486 Taylor ampFrancis 2013
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[30] L M Colla A L Muccillo-Baisch and J A Vieira CostaldquoSpirulina platensis effects on the levels of total cholesterol HDLand triacylglycerols in rabbits fed with a hypercholesterolemicdietrdquo Brazilian Archives of Biology and Technology vol 51 no 2pp 405ndash411 2008
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[79] I Rodrıguez-Meizoso L Jaime S Santoyo F J Senorans ACifuentes and E Ibanez ldquoSubcritical water extraction andcharacterization of bioactive compounds from Haematococcuspluvialis microalgardquo Journal of Pharmaceutical and BiomedicalAnalysis vol 51 no 2 pp 456ndash463 2010
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production of bioactive compounds from Tetraselmis suecica atpilot scalerdquo Journal of Cleaner Production vol 64 pp 323ndash3312014
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[97] T Tannin-Spitz M Bergman D Van-Moppes S Grossmanand S Arad ldquoAntioxidant activity of the polysaccharide of thered microalga Porphyridium sprdquo Journal of Applied Phycologyvol 17 no 3 pp 215ndash222 2005
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[99] H M Amaro A C Guedes and F X Malcata ldquoAntimicrobialactivities of microalgae an invited reviewrdquo in Science againstMicrobial Pathogens Communicating Current Research andTechnological Advances A Mendez-Vilas Ed pp 1272ndash12802011
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[102] M F De Jesus Raposo R M S C De Morais and A M M BDe Morais ldquoHealth applications of bioactive compounds frommarine microalgaerdquo Life Sciences vol 93 no 15 pp 479ndash4862013
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[106] M G de Morais C Stillings R Dersch et al ldquoPreparation ofnanofibers containing the microalga Spirulina (Arthrospira)rdquoBioresource Technology vol 101 no 8 pp 2872ndash2876 2010
[107] D Steffens M Lersch A Rosa et al ldquoA new biomaterialof nanofibers with the microalga Spirulina as scaffolds tocultivate with stem cells for use in tissue engineeringrdquo Journalof Biomedical Nanotechnology vol 9 no 4 pp 710ndash718 2013
[108] C Barrow and F ShahidiMarine Nutraceuticals and FunctionalFoods CRC Press Taylor amp Francis Boca Raton Fla USA2008
[109] M N A Khan J-Y ChoM-C Lee et al ldquoIsolation of two anti-inflammatory and one pro-inflammatory polyunsaturated fattyacids from the brown seaweed Undaria pinnatifidardquo Journal ofAgricultural and Food Chemistry vol 55 no 17 pp 6984ndash69882007
[110] M S Matsui N Muizzuddin S Arad and K MarenusldquoSulfated polysaccharides from redmicroalgae have antiinflam-matory properties in vitro and in vivordquo Applied Biochemistryand Biotechnology vol 104 no 1 pp 13ndash22 2003
[111] V B Bhat and K M Madyastha ldquoScavenging of peroxynitriteby phycocyanin and phycocyanobilin from Spirulina platensisprotection against oxidative damage to DNArdquo Biochemical andBiophysical Research Communications vol 285 no 2 pp 262ndash266 2001
[112] I A Schepetkin and M T Quinn ldquoBotanical polysaccharidesmacrophage immunomodulation and therapeutic potentialrdquoInternational Immunopharmacology vol 6 no 3 pp 317ndash3332006
[113] J K Park Z-H Kim C G Lee et al ldquoCharacterization andimmunostimulating activity of a water-soluble polysaccharideisolated from Haematococcus lacustrisrdquo Biotechnology and Bio-process Engineering vol 16 no 6 pp 1090ndash1098 2011
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[115] E Ryckebosch C Bruneel R Termote-Verhalle K Goiris KMuylaert and I Foubert ldquoNutritional evaluation of microalgaeoils rich in omega-3 long chain polyunsaturated fatty acids as analternative for fish oilrdquo Food Chemistry vol 160 pp 393ndash4002014
[116] P Zhao Z Zang X Xie A Huang and G Wang ldquoTheinfluence of different flocculants on the physiological activityand fucoxanthin production of Phaeodactylum tricornutumrdquoProcess Biochemistry vol 49 no 4 pp 681ndash687 2014
[117] D Moreau C Tomasoni C Jacquot et al ldquoCultivated microal-gae and the carotenoid fucoxanthin from Odontella auritaas potent anti-proliferative agents in bronchopulmonary andepithelial cell linesrdquo Environmental Toxicology and Pharmacol-ogy vol 22 no 1 pp 97ndash103 2006
[118] H Maeda M Hosokawa T Sashima K Funayama and KMiyashita ldquoFucoxanthin from edible seaweed Undaria pinnati-fida shows antiobesity effect through UCP1 expression in whiteadipose tissuesrdquo Biochemical and Biophysical Research Commu-nications vol 332 no 2 pp 392ndash397 2005
[119] J E Piero Estrada P Bermejo Bescos and A M Villar delFresno ldquoAntioxidant activity of different fractions of Spirulinaplatensis protean extractrdquo IL Farmaco vol 56 no 5ndash7 pp 497ndash500 2001
[120] S-M Kang S-J Heo K-N Kim S-H Lee and Y-JJeon ldquoIsolation and identification of new compound 2710158401015840-phloroglucinol-661015840-bieckol from brown algae Ecklonia cavaand its antioxidant effectrdquo Journal of Functional Foods vol 4no 1 pp 158ndash166 2012
[121] HHAbdEl-Baky F K El Baz andG S El-Baroty ldquoProductionof phenolic compounds from Spirulinamaximamicroalgae andits protective effectsrdquoAfrican Journal of Biotechnology vol 8 no24 pp 7059ndash7067 2009
[122] A C Guedes H M Amaro and F X Malcata ldquoMicroalgae assources of carotenoidsrdquoMarineDrugs vol 9 no 4 pp 625ndash6442011
[123] G L Renju G M Kurup and K C H Saritha ldquoEffect oflycopene from Chlorella marina on high cholesterol-inducedoxidative damage and inflammation in ratsrdquo Inflammopharma-cology vol 22 no 1 pp 45ndash54 2014
[124] G L Renju G M Kurup and C H S Kumari ldquoAnti-inflammatory activity of lycopene isolated from Chlorellamarina onType II Collagen induced arthritis in SpragueDawleyratsrdquo Immunopharmacology and Immunotoxicology vol 35 no2 pp 282ndash291 2013
[125] C Vılchez E Forjan M Cuaresma F Bedmar I Garbayo andJ M Vega ldquoMarine carotenoids biological functions andcommercial applicationsrdquo Marine Drugs vol 9 no 3 pp 319ndash333 2011
[126] G Richardson ldquoBeyond eye healthrdquo Life Extension Magazine2011 httpwwwleforgMagazine20117Beyond-Eye-HealthPage-01
[127] M Abidov Z Ramazanov R Seifulla and S Grachev ldquoTheeffects of Xanthigen in the weight management of obesepremenopausal women with non-alcoholic fatty liver diseaseand normal liver fatrdquo Diabetes Obesity and Metabolism vol 12no 1 pp 72ndash81 2010
[128] H M Ragap R H Khalil and H HMutawie ldquoImmunostimu-lant effects of dietary Spirulina platensis on tilapia Oreochromisniloticusrdquo Journal of Applied Pharmaceutical Science vol 2 no2 pp 26ndash31 2012
[129] W Xu Z Gao Z Qi M Qiu J-Q Peng and R Shao ldquoEffect ofdietary chlorella on the growth performance and physiologicalparameters of gibel carp Carassius auratus gibeliordquo TurkishJournal of Fisheries and Aquatic Sciences vol 14 no 1 pp 53ndash572014
[130] P Amaninejad H Emadi M Ematiazjoo et al ldquoEffects ofDunaliella microalgae (Dunaliella salina) on different level of
BioMed Research International 15
IgM Immunoglobulin in rainbow trout (Oncrohynchusmykiss)rdquoGlobal Journal of Biodiversity Science and Management vol 3no 2 pp 237ndash242 2013
[131] V Mimouni L Ulmann V Pasquet et al ldquoThe potential ofmicroalgae for the production of bioactive molecules of phar-maceutical interestrdquoCurrent Pharmaceutical Biotechnology vol13 no 15 pp 2733ndash2750 2012
[132] S M Tosh and S Yada ldquoDietary fibres in pulse seeds and frac-tions characterization functional attributes and applicationsrdquoFood Research International vol 43 no 2 pp 450ndash460 2010
[133] H M Amaro R Barros A C Guedes I Sousa-Pinto and FXMalcata ldquoMicroalgal compoundsmodulate carcinogenesis inthe gastrointestinal tractrdquo Trends in Biotechnology vol 31 no 2pp 92ndash98 2013
[134] S S M Mostafa ldquoMicroalgal biotechnology prospects andapplicationsrdquo in Plant Science chapter 12 pp 275ndash314 InTech2012
[135] L Custodio T Justo L Silvestre et al ldquoMicroalgae of dif-ferent phyla display antioxidant metal chelating and acetyl-cholinesterase inhibitory activitiesrdquoFoodChemistry vol 131 no1 pp 134ndash140 2012
[136] C-CHu J-T Lin F-J Lu F-P Chou andD-J Yang ldquoDetermi-nation of carotenoids in Dunaliella salina cultivated in Taiwanand antioxidant capacity of the algal carotenoid extractrdquo FoodChemistry vol 109 no 2 pp 439ndash446 2008
biomass that may exert a protective function in the bodywhen consumed as food or used as pharmaceuticals andcosmetics
Because of its anti-inflammatory capabilities microalgalbiomass is being considered for applications in tissue engi-neering for the development of scaffolds for use in reconsti-tution of organs and tissues [105 106] This is an importantapplication for humans especially in patients with burnsin which the skin was completely lost [107] Among themost important microalgal compounds with such prop-erties are long-chain polyunsaturated fatty acids (PUFAs)[108 109] sulfurized polysaccharides [110] and pigments[111]
Many microalgal polysaccharides possess the ability tomodulate the immune system through the activation ofmacrophage functions and the induction of reactive oxy-gen species (ROS) nitric oxide (NO) and various othertypes of cytokineschemokines [112] Macrophages are ableto regulate several innate responses and secrete cytokinesand chemocytokines that serve as signals for immune andinflammatory molecular reactions [113] Sulfur polysaccha-rides with anti-inflammatory activity can be applied inskin treatments inhibiting the migration and adhesion ofpolymorphonuclear leukocytes [110] Guzman et al [114]studied the anti-inflammatory capacity of the microalgaChlorella stigmatophora and Phaeodactylum tricomutum andconcluded that bothmicroalgae showed positive responses inthe test of paw edema by carrageenan
The PUFAs especially 1205963 and 1205966 as eicosapentaenoic(EPA) docosahexaenoic (DHA) and arachidonic (AA) acidshave been applied in the treatment of chronic inflammationsuch as rheumatism and skin diseases [108] Ryckebosch etal [115] evaluated the nutritional value of the total lipidsextracted from different PUFAs produced by microalgae Inthis study the microalgae IsochrysisNannochloropsis Phaeo-dactylum Pavlova and Thalassiosira produced 1205963 PUFA asan alternative to fish oil in food
Among the pigments with anti-inflammatory activityfucoxanthin carotenoid found in diatoms [116 117] is capableof stimulating apoptosis in human cancer cells [118] A phy-cocyanin found in cyanobacteria has an anti-inflammatoryactivity that occurs through the inhibition of histaminerelease [111 119]
54 Compounds with Potentiality over Degenerative Dis-eases In humans the oxidation reactions driven by reactiveoxygen species (ROS) can lead to irreversible damage tocellular components including lipids proteins and DNAdegradation andor mutation Consequently this damagecan lead to several syndromes such as cardiovascular dis-ease some cancers and the degenerative diseases of aging[120]
Chronic age-related diseases involve oxidative stress andinflammation and their consequences Chronic inflammationplays a significant role in the mediation of neurodegenerativediseases such as Parkinsonrsquos disease Alzheimerrsquos diseasemultiple sclerosis acquired immunodeficiency syndrome(AIDS) and dementia complex [77]
Natural pigments derived from microalgae (NPs) haveneuroprotective properties being valuable sources as func-tional ingredients in foods and pharmaceutical products thatshow efficient action in the treatment andor prevention ofneurodegenerative diseases Vitamin E has preventive effectsfor many diseases such as atherosclerosis and heart diseaseas well as neurodegenerative diseases such as multiplesclerosis [77]
Carotenoids have great potential benefits to humanhealth including the treatment of degenerative diseases suchas macular degeneration and cataract development Thesecompounds act as antioxidants reducing oxidative damageby ROS Studies indicated that increased intake of phenolsdecreased the occurrence of degenerative diseases Phenoliccompounds from microalgae with the potential to fight freeradicals have been reported [121]
Dunaliella salina is a natural source of 120573-carotene whichproduced a reduced risk of cancer and degenerative diseasesin humans Lutein is effective against various diseases includ-ing cataracts and macular degeneration and in the earlystages of atherosclerosis Extracts of Chlorella sp containing120573-carotene and lutein significantly prevented the cognitivedisability that accompanies Alzheimerrsquos disease in rats It wasalso reported that lutein extracted from Chlorella reducedthe incidence of cancer Likewise carotenoids extractedfrom Chlorella ellipsoidea and Chlorella vulgaris inhibited thegrowth of colon cancer [122] A lycopene extracted fromthe microalgae Chlorella marina significantly reduced theproliferation of prostate cancer inmice [123]This compoundalso reduced total cholesterol and low-density lipoprotein(LDL) levels [123] and improved rheumatoid arthritis [124]
Low plasma levels of lutein have also been associatedwith an increased tendency ofmyocardial infarction whereashigh intake of lutein was related to a decreased risk ofstroke In addition high levels of carotenoids with provi-tamin A activity including 120572-carotene 120573-carotene and 120573-cryptoxanthin have been associated with reduction in therisk of angina pectoris Macular degeneration the lead-ing cause of irreversible vision loss has also been associ-ated with very low consumption of lutein and zeaxanthin[125]
Scientific findings indicate astaxanthin for multimodalintervention formany forms of degenerative diseases includ-ing cardiovascular diseases cancer metabolic syndromecognitive impairment age-related immune dysfunctionstomach and ocular diseases (macular degeneration cataractglaucoma diabetic retinopathy and retinitis pigmentosa)and skin damage [126] High levels of lycopene in plasmaand tissues were inversely related to coronary heart diseasemyocardial infarction and the risk of atherosclerosis [125]
55 Compounds withHealth Promoting Function The impor-tance of microalgae as sources of functional ingredients hasbeen recognized because of their beneficial health effectsNatural pigments are valuable sources of bioactive com-pounds These pigments have various beneficial biologicalactivities such as antioxidant anticancer anti-inflammatoryantiobesity antiangiogenic and neuroprotective action and
10 BioMed Research International
are indicated for the treatment or prevention of severalchronic diseases [77]
The antioxidant potential of carotenoid pigments andtheir ability to prevent cancer aging atherosclerosis coro-nary heart disease and degenerative diseases have beendescribed 120573-Carotene has higher provitamin A activitywhich is essential for vision and the correct functioning ofthe immune system Astaxanthin is linked to many healthbenefits such as protection against lipid peroxidation age-related macular degeneration reduced atherosclerosis andan increased immune response [102]
Fucoxanthin is considered as a promising dietary andweight loss supplement and for the treatment of obesityClinical studies by Abidov et al [127] demonstrated the effectof ldquoxanthigenrdquo a fucoxanthin based antiobesity supplementFurthermore fucoxanthinmay be useful for the prevention ofbone diseases such as osteoporosis and rheumatoid arthritisIt has also been reported to be effective for the therapeutictreatment of diabetic diseases suppressing insulin and hyper-glycemia [77]
Microalgae proteins are of great interest as a source ofbioactive peptides due to their therapeutic potential in thetreatment of various diseases [7] Proteins peptides andamino acids have functions that contribute to health benefitsThese compounds can include growth factors hormones andimmunomodulators and can help to replace damaged tissuesin addition to providing nutritional benefits Microalgaesuch as Chlorella and Spirulina (Arthrospira) may be usedas nutraceuticals or included in functional foods to preventdiseases and damage to cells and tissues due to their richprotein content and amino acid profile [102]
The antimicrobial action of certain enzymes (eglysozyme) and immunoglobulins has been reported andrecommended for people with different diseases (egCrohnrsquos disease) due to the existence of formulations withpeptides and free amino acids Studies of the healtheffects of lysozyme have been reported in the microalgaeSpirulina platensis [128] Chlorella [129] and Dunaliellasalina [130] Spirulina (Arthrospira) and Chlorella biomasspills are marketed as is ldquoHawaiian Spirulina Pacificardquo(httpspirulinagreennutritionalscomau) Other proteinscan also increase the production of cholecystokinin involvedin appetite suppression and the reduction of LDL-cholesterolProtein peptides from Chlorella have a potential as dietarysupplements for the prevention of oxidative stress-relateddiseases such as atherosclerosis coronary heart disease andcancer [39]
The essential fatty acids 120596-3 and 120596-6 in particular areimportant for the integrity of tissues 120574-Linolenic acid hastherapeutic applications in cosmetics to revitalize the skinand thus slow aging Linoleic and linolenic acids are essentialnutrients for the immune system and other related tissueregeneration processes Linoleic acid is also used for thetreatment of hyperplasia of the skin [102]
The most studied microalgal lipid compounds are thepolyunsaturated fatty acids (PUFAs) docosahexaenoic acid(120596-3 C226) (DHA) eicosapentaenoic acid (C20 120596-35)(EPA) and arachidonic acid (120596-6 C204) (ARA) Studies haveshown that dietary120596-3 PUFAs have a protective effect against
atherosclerotic heart disease [131] DHA and EPA showed theability to reduce problems associated with strokes and arthri-tis besides reducing hypertension lipid content (a decreasein triglycerides and an increase of HDL) and acting asanti-inflammatory agents DHA is also important in thedevelopment and function of the nervous system Further-more ARA and EPA are platelet aggregators vasoconstric-tors and vasodilators and have antiaggregative action on theendothelium as well as chemostatic activity in neutrophils[102]
Other lipid compounds with interesting bioactive prop-erties are the microalgal sterols Phytosterols have demon-strated reduction of total cholesterol (LDL) in humans byinhibiting its absorption from the intestine [50] Polysac-charides can be considered as dietary fibers associatedwith different physiological effects Insoluble fiber (cellulosehemicellulose and lignin) mainly promotes the movementof material through the digestive system thereby improvinglaxation and increasing satietyThey can also be considered asprebiotics because they promote the growth of gutmicrofloraincluding probiotic species Soluble fiber (oligosaccharidespectins and 120573-glucans) may reduce cholesterol and regulateblood glucose [7 132]
6 Conclusion
The proven ability of microalgae to produce bioactive com-pounds places these microorganisms in the biotechnologicalspotlight for applications in various areas of study especiallyin the life sciencesThe production ofmicroalgal metaboliteswhich stimulate defense mechanisms in the human bodyhas spurred intense study of the application of microalgalbiomass in various foods and pharmacological and medicalproducts There is obviously a need for further study of theidentified compounds and their activities in the treatmentand prevention of various diseases in addition to an ongoingsearch for other as yet undetected metabolites
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgment
The authors thank the National Counsel of Technologicaland Scientific Development (CNPq) for the Productivityin Technological Development and Innovative ExtensionScholarship
References
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[2] A A El Gamal ldquoBiological importance of marine algaerdquo SaudiPharmaceutical Journal vol 18 no 1 pp 1ndash25 2010
BioMed Research International 11
[3] I Moreno-Garrido ldquoMicroalgae immobilization current tech-niques and usesrdquo Bioresource Technology vol 99 no 10 pp3949ndash3964 2008
[4] R-B Volk and F H Furkert ldquoAntialgal antibacterial andantifungal activity of two metabolites produced and excretedby cyanobacteria during growthrdquoMicrobiological Research vol161 no 2 pp 180ndash186 2006
[5] R-B Volk ldquoA newly developed assay for the quantitativedetermination of antimicrobial (anticyanobacterial) activity ofboth hydrophilic and lipophilic test compounds without anyrestrictionrdquoMicrobiological Research vol 163 no 2 pp 161ndash1672008
[6] D F Smee K W Bailey M-H Wong et al ldquoTreatment ofinfluenza A (H1N1) virus infections in mice and ferrets withcyanovirin-Nrdquo Antiviral Research vol 80 no 3 pp 266ndash2712008
[7] E Ibanez and A Cifuentes ldquoBenefits of using algae as naturalsources of functional ingredientsrdquo Journal of the Science of Foodand Agriculture vol 93 no 4 pp 703ndash709 2013
[8] G Markou and E Nerantzis ldquoMicroalgae for high-valuecompounds and biofuels production a review with focus oncultivation under stress conditionsrdquo Biotechnology Advancesvol 31 no 8 pp 1532ndash1542 2013
[9] R Harun M Singh G M Forde andM K Danquah ldquoBiopro-cess engineering ofmicroalgae to produce a variety of consumerproductsrdquo Renewable and Sustainable Energy Reviews vol 14no 3 pp 1037ndash1047 2010
[10] C Kolympiris N Kalaitzandonakes and D Miller ldquoPublicfunds and local biotechnology firm creationrdquo Research Policyvol 43 no 1 pp 121ndash137 2014
[11] S Bhagavathy P Sumathi and I Jancy Sherene Bell ldquoGreenalgae Chlorococcum humicola-a new source of bioactive com-pounds with antimicrobial activityrdquo Asian Pacific Journal ofTropical Biomedicine vol 1 no 1 pp S1ndashS7 2011
[12] A M F Palavra J P Coelho J G Barroso et al ldquoSupercrit-ical carbon dioxide extraction of bioactive compounds frommicroalgae and volatile oils from aromatic plantsrdquo Journal ofSupercritical Fluids vol 60 pp 21ndash27 2011
[13] I Priyadarshani and B Rath ldquoCommercial and industrialapplications of micro algaemdasha reviewrdquo Journal of Algal BiomassUtilization vol 3 no 4 pp 89ndash100 2012
[14] JW Blunt B R CoppM H GMunro P T Northcote andMR Prinsep ldquoMarine natural productsrdquoNatural Product Reportsvol 23 no 1 pp 26ndash78 2006
[15] A M S Mayer and M T Hamann ldquoMarine pharmacologyin 2001-2002 marine compounds with anthelmintic antibacte-rial anticoagulant antidiabetic antifungal anti-inflammatoryantimalarial antiplatelet antiprotozoal antituberculosis andantiviral activities affecting the cardiovascular immune andnervous systems and other miscellaneous mechanisms ofactionrdquo Comparative Biochemistry and Physiology Part C Toxi-cology amp Pharmacology vol 140 no 3-4 pp 265ndash286 2005
[16] M Plaza S Santoyo L Jaime et al ldquoScreening for bioactivecompounds from algaerdquo Journal of Pharmaceutical and Biomed-ical Analysis vol 51 no 2 pp 450ndash455 2010
[17] I Rodrıguez-Meizoso L Jaime S Santoyo et al ldquoPressurizedfluid extraction of bioactive compounds from Phormidiumspeciesrdquo Journal of Agricultural and Food Chemistry vol 56 no10 pp 3517ndash3523 2008
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vivo and in vitro aspectsrdquo Brazilian Journal of Pharmacognosyvol 23 no 3 pp 471ndash480 2013
[19] B Nobre FMarcelo R Passos et al ldquoSupercritical carbon diox-ide extraction of astaxanthin and other carotenoids from themicroalga Haematococcus pluvialisrdquo European Food Researchand Technology vol 223 no 6 pp 787ndash790 2006
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extraction of 120574-linolenic acid and other lipids from Arthrospira(Spirulina)maxima comparison with organic solvent extrac-tionrdquo Food Chemistry vol 99 no 1 pp 57ndash63 2006
[21] I Romano M R Bellitti B Nicolaus et al ldquoLipid profilea useful chemotaxonomic marker for classification of a newcyanobacterium in Spirulina genusrdquo Phytochemistry vol 54 no3 pp 289ndash294 2000
[22] J A C Costa and M G Morais ldquoMicroalgae for food produc-tionrdquo in Fermentation Process Engineering in the Food IndustryC R Soccol A Pandey and C Larroche Eds p 486 Taylor ampFrancis 2013
[23] MAAmbrosi CO Reinehr T E Bertolin et al ldquoPropriedadesde saude de Spirulina spprdquo Revista de Ciencias FarmaceuticasBasica e Aplicada vol 29 no 2 pp 109ndash117 2008
[24] J A Borges G M Rosa L H R Meza A A Henrard M RA Z Souza and J A V Costa ldquoSpirulina sp LEB-18 cultureusing effluent from the anaerobic digestionrdquo Brazilian Journalof Chemical Engineering vol 30 no 2 pp 277ndash287 2013
[25] F S Antelo J A V Costa and S J Kalil ldquoThermal degradationkinetics of the phycocyanin from Spirulina platensisrdquo Biochem-ical Engineering Journal vol 41 no 1 pp 43ndash47 2008
[26] S T Silveira J F M Burkert J A V Costa C A V Burkertand S J Kalil ldquoOptimization of phycocyanin extraction fromSpirulina platensis using factorial designrdquo Bioresource Technol-ogy vol 98 no 8 pp 1629ndash1634 2007
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[30] L M Colla A L Muccillo-Baisch and J A Vieira CostaldquoSpirulina platensis effects on the levels of total cholesterol HDLand triacylglycerols in rabbits fed with a hypercholesterolemicdietrdquo Brazilian Archives of Biology and Technology vol 51 no 2pp 405ndash411 2008
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[39] M Plaza M Herrero A Alejandro Cifuentes and E IbanezldquoInnovative natural functional ingredients from microalgaerdquoJournal of Agricultural and Food Chemistry vol 57 no 16 pp7159ndash7170 2009
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[79] I Rodrıguez-Meizoso L Jaime S Santoyo F J Senorans ACifuentes and E Ibanez ldquoSubcritical water extraction andcharacterization of bioactive compounds from Haematococcuspluvialis microalgardquo Journal of Pharmaceutical and BiomedicalAnalysis vol 51 no 2 pp 456ndash463 2010
[80] M Herrero M Castro-Puyana J A Mendiola and E IbanezldquoCompressed fluids for the extraction of bioactive compoundsrdquoTrends in Analytical Chemistry vol 43 pp 67ndash83 2013
[81] N K Singh and D W Dhar ldquoMicroalgae as second generationbiofuel A reviewrdquo Agronomy for Sustainable Development vol31 no 4 pp 605ndash629 2011
[82] L Brennan and P Owende ldquoBiofuels frommicroalgae towardsmeeting advanced fuel standardsrdquo in Advanced Biofuels andBioproducts JW Lee Ed pp 553ndash599 Springer NewYork NYUSA 2013
[83] A Singh P S Nigam and J D Murphy ldquoRenewable fuels fromalgae an answer to debatable land based fuelsrdquo BioresourceTechnology vol 102 no 1 pp 10ndash16 2011
[84] P Perez-Lopez S Gonzalez-Garcıa R G Ulloa J SineiroG Feijoo and M T Moreira ldquoLife cycle assessment of the
production of bioactive compounds from Tetraselmis suecica atpilot scalerdquo Journal of Cleaner Production vol 64 pp 323ndash3312014
[85] B Subhadra ldquoAlgal biorefinery-based industry an approachto address fuel and food insecurity for a carbon-smart worldrdquoJournal of the Science of Food and Agriculture vol 91 no 1 pp2ndash13 2011
[86] D J Newman and G M Cragg ldquoNatural products as sourcesof new drugs over the 30 years from 1981 to 2010rdquo Journal ofNatural Products vol 75 no 3 pp 311ndash335 2012
[87] H-B Li K-W Cheng C-C Wong K-W Fan F Chen andY Jiang ldquoEvaluation of antioxidant capacity and total phenoliccontent of different fractions of selected microalgaerdquo FoodChemistry vol 102 no 3 pp 771ndash776 2007
[88] T M Mata A A Martins and N S Caetano ldquoMicroalgaefor biodiesel production and other applications a reviewrdquoRenewable and Sustainable EnergyReviews vol 14 no 1 pp 217ndash232 2010
[89] A Gupta and J K Sainis ldquoIsolation of C-phycocyanin fromSynechococcus sp (Anacystis nidulans BD1)rdquo Journal of AppliedPhycology vol 22 no 3 pp 231ndash233 2010
[90] P J Viskari and C L Colyer ldquoRapid extraction of phyco-biliproteins from cultured cyanobacteria samplesrdquo AnalyticalBiochemistry vol 319 no 2 pp 263ndash271 2003
[91] R Bermejo Roman J M Alvarez-Pez F G Acien Fernandezand E Molina Grima ldquoRecovery of pure B-phycoerythrin fromthe microalga Porphyridium cruentumrdquo Journal of Biotechnol-ogy vol 93 no 1 pp 73ndash85 2002
[92] C I Cazzonelli ldquoCarotenoids in nature insights from plantsand beyondrdquo Functional Plant Biology vol 38 no 11 pp 833ndash847 2011
[93] M A Hejazi and R HWijffels ldquoMilking of microalgaerdquo Trendsin Biotechnology vol 22 no 4 pp 189ndash194 2004
[94] S Arad and O Levy-Ontman ldquoRed microalgal cell-wallpolysaccharides biotechnological aspectsrdquo Current Opinion inBiotechnology vol 21 no 3 pp 358ndash364 2010
[95] M Kim J H Yim S-Y Kim et al ldquoIn vitro inhibitionof influenza A virus infection by marine microalga-derivedsulfated polysaccharide p-KG03rdquoAntiviral Research vol 93 no2 pp 253ndash259 2012
[96] Z A Mohamed ldquoPolysaccharides as a protective responseagainst microcystin-induced oxidative stress in Chlorella vul-garis and Scenedesmus quadricauda and their possible signifi-cance in the aquatic ecosystemrdquo Ecotoxicology vol 17 no 6 pp504ndash516 2008
[97] T Tannin-Spitz M Bergman D Van-Moppes S Grossmanand S Arad ldquoAntioxidant activity of the polysaccharide of thered microalga Porphyridium sprdquo Journal of Applied Phycologyvol 17 no 3 pp 215ndash222 2005
[98] J W Prakash M Johnson and S Jeeva ldquoAntimicrobial activityof certain fresh water microalgae from Thamirabarani RiverTamil Nadu South Indiardquo Asian Pacific Journal of TropicalBiomedicine vol 1 supplement no 2 pp S170ndashS173 2011
[99] H M Amaro A C Guedes and F X Malcata ldquoAntimicrobialactivities of microalgae an invited reviewrdquo in Science againstMicrobial Pathogens Communicating Current Research andTechnological Advances A Mendez-Vilas Ed pp 1272ndash12802011
[100] V J Smith A PDesbois and E ADyrynda ldquoConventional andunconventional antimicrobials from fish marine invertebratesand micro-algaerdquo Marine Drugs vol 8 no 4 pp 1213ndash12622010
14 BioMed Research International
[101] M F D J Raposo A M M B de Morais and R M SC de Morais ldquoInfluence of sulphate on the composition andantibacterial and antiviral properties of the exopolysaccharidefrom Porphyridium cruentumrdquo Life Sciences vol 101 no 1-2 pp56ndash63 2014
[102] M F De Jesus Raposo R M S C De Morais and A M M BDe Morais ldquoHealth applications of bioactive compounds frommarine microalgaerdquo Life Sciences vol 93 no 15 pp 479ndash4862013
[103] A Smelcerovic Z Knezevic-Jugovic and Z PetronijevicldquoMicrobial polysaccharides and their derivatives as current andprospective pharmaceuticalsrdquo Current Pharmaceutical Designvol 14 no 29 pp 3168ndash3195 2008
[104] M T Madigan J M Martinko P V Dunlap and D P ClarkMicrobiologia de Brock Artmed Editora 12th edition 2010
[105] M G de Morais J A V Costa P H L Pranke et alldquoDevelopment of a newnanofiber scaffold for usewith stemcellsin a third degree burn animal modelrdquo Burns Oxford vol 40 no8 pp 1650ndash1660 2014
[106] M G de Morais C Stillings R Dersch et al ldquoPreparation ofnanofibers containing the microalga Spirulina (Arthrospira)rdquoBioresource Technology vol 101 no 8 pp 2872ndash2876 2010
[107] D Steffens M Lersch A Rosa et al ldquoA new biomaterialof nanofibers with the microalga Spirulina as scaffolds tocultivate with stem cells for use in tissue engineeringrdquo Journalof Biomedical Nanotechnology vol 9 no 4 pp 710ndash718 2013
[108] C Barrow and F ShahidiMarine Nutraceuticals and FunctionalFoods CRC Press Taylor amp Francis Boca Raton Fla USA2008
[109] M N A Khan J-Y ChoM-C Lee et al ldquoIsolation of two anti-inflammatory and one pro-inflammatory polyunsaturated fattyacids from the brown seaweed Undaria pinnatifidardquo Journal ofAgricultural and Food Chemistry vol 55 no 17 pp 6984ndash69882007
[110] M S Matsui N Muizzuddin S Arad and K MarenusldquoSulfated polysaccharides from redmicroalgae have antiinflam-matory properties in vitro and in vivordquo Applied Biochemistryand Biotechnology vol 104 no 1 pp 13ndash22 2003
[111] V B Bhat and K M Madyastha ldquoScavenging of peroxynitriteby phycocyanin and phycocyanobilin from Spirulina platensisprotection against oxidative damage to DNArdquo Biochemical andBiophysical Research Communications vol 285 no 2 pp 262ndash266 2001
[112] I A Schepetkin and M T Quinn ldquoBotanical polysaccharidesmacrophage immunomodulation and therapeutic potentialrdquoInternational Immunopharmacology vol 6 no 3 pp 317ndash3332006
[113] J K Park Z-H Kim C G Lee et al ldquoCharacterization andimmunostimulating activity of a water-soluble polysaccharideisolated from Haematococcus lacustrisrdquo Biotechnology and Bio-process Engineering vol 16 no 6 pp 1090ndash1098 2011
[114] S Guzman A Gato M Lamela M Freire-Garabal and J MCalleja ldquoAnti-inflammatory and immunomodulatory activitiesof polysaccharide from Chlorella stigmatophora and Phaeo-dactylum tricornutumrdquo Phytotherapy Research vol 17 no 6 pp665ndash670 2003
[115] E Ryckebosch C Bruneel R Termote-Verhalle K Goiris KMuylaert and I Foubert ldquoNutritional evaluation of microalgaeoils rich in omega-3 long chain polyunsaturated fatty acids as analternative for fish oilrdquo Food Chemistry vol 160 pp 393ndash4002014
[116] P Zhao Z Zang X Xie A Huang and G Wang ldquoTheinfluence of different flocculants on the physiological activityand fucoxanthin production of Phaeodactylum tricornutumrdquoProcess Biochemistry vol 49 no 4 pp 681ndash687 2014
[117] D Moreau C Tomasoni C Jacquot et al ldquoCultivated microal-gae and the carotenoid fucoxanthin from Odontella auritaas potent anti-proliferative agents in bronchopulmonary andepithelial cell linesrdquo Environmental Toxicology and Pharmacol-ogy vol 22 no 1 pp 97ndash103 2006
[118] H Maeda M Hosokawa T Sashima K Funayama and KMiyashita ldquoFucoxanthin from edible seaweed Undaria pinnati-fida shows antiobesity effect through UCP1 expression in whiteadipose tissuesrdquo Biochemical and Biophysical Research Commu-nications vol 332 no 2 pp 392ndash397 2005
[119] J E Piero Estrada P Bermejo Bescos and A M Villar delFresno ldquoAntioxidant activity of different fractions of Spirulinaplatensis protean extractrdquo IL Farmaco vol 56 no 5ndash7 pp 497ndash500 2001
[120] S-M Kang S-J Heo K-N Kim S-H Lee and Y-JJeon ldquoIsolation and identification of new compound 2710158401015840-phloroglucinol-661015840-bieckol from brown algae Ecklonia cavaand its antioxidant effectrdquo Journal of Functional Foods vol 4no 1 pp 158ndash166 2012
[121] HHAbdEl-Baky F K El Baz andG S El-Baroty ldquoProductionof phenolic compounds from Spirulinamaximamicroalgae andits protective effectsrdquoAfrican Journal of Biotechnology vol 8 no24 pp 7059ndash7067 2009
[122] A C Guedes H M Amaro and F X Malcata ldquoMicroalgae assources of carotenoidsrdquoMarineDrugs vol 9 no 4 pp 625ndash6442011
[123] G L Renju G M Kurup and K C H Saritha ldquoEffect oflycopene from Chlorella marina on high cholesterol-inducedoxidative damage and inflammation in ratsrdquo Inflammopharma-cology vol 22 no 1 pp 45ndash54 2014
[124] G L Renju G M Kurup and C H S Kumari ldquoAnti-inflammatory activity of lycopene isolated from Chlorellamarina onType II Collagen induced arthritis in SpragueDawleyratsrdquo Immunopharmacology and Immunotoxicology vol 35 no2 pp 282ndash291 2013
[125] C Vılchez E Forjan M Cuaresma F Bedmar I Garbayo andJ M Vega ldquoMarine carotenoids biological functions andcommercial applicationsrdquo Marine Drugs vol 9 no 3 pp 319ndash333 2011
[126] G Richardson ldquoBeyond eye healthrdquo Life Extension Magazine2011 httpwwwleforgMagazine20117Beyond-Eye-HealthPage-01
[127] M Abidov Z Ramazanov R Seifulla and S Grachev ldquoTheeffects of Xanthigen in the weight management of obesepremenopausal women with non-alcoholic fatty liver diseaseand normal liver fatrdquo Diabetes Obesity and Metabolism vol 12no 1 pp 72ndash81 2010
[128] H M Ragap R H Khalil and H HMutawie ldquoImmunostimu-lant effects of dietary Spirulina platensis on tilapia Oreochromisniloticusrdquo Journal of Applied Pharmaceutical Science vol 2 no2 pp 26ndash31 2012
[129] W Xu Z Gao Z Qi M Qiu J-Q Peng and R Shao ldquoEffect ofdietary chlorella on the growth performance and physiologicalparameters of gibel carp Carassius auratus gibeliordquo TurkishJournal of Fisheries and Aquatic Sciences vol 14 no 1 pp 53ndash572014
[130] P Amaninejad H Emadi M Ematiazjoo et al ldquoEffects ofDunaliella microalgae (Dunaliella salina) on different level of
BioMed Research International 15
IgM Immunoglobulin in rainbow trout (Oncrohynchusmykiss)rdquoGlobal Journal of Biodiversity Science and Management vol 3no 2 pp 237ndash242 2013
[131] V Mimouni L Ulmann V Pasquet et al ldquoThe potential ofmicroalgae for the production of bioactive molecules of phar-maceutical interestrdquoCurrent Pharmaceutical Biotechnology vol13 no 15 pp 2733ndash2750 2012
[132] S M Tosh and S Yada ldquoDietary fibres in pulse seeds and frac-tions characterization functional attributes and applicationsrdquoFood Research International vol 43 no 2 pp 450ndash460 2010
[133] H M Amaro R Barros A C Guedes I Sousa-Pinto and FXMalcata ldquoMicroalgal compoundsmodulate carcinogenesis inthe gastrointestinal tractrdquo Trends in Biotechnology vol 31 no 2pp 92ndash98 2013
[134] S S M Mostafa ldquoMicroalgal biotechnology prospects andapplicationsrdquo in Plant Science chapter 12 pp 275ndash314 InTech2012
[135] L Custodio T Justo L Silvestre et al ldquoMicroalgae of dif-ferent phyla display antioxidant metal chelating and acetyl-cholinesterase inhibitory activitiesrdquoFoodChemistry vol 131 no1 pp 134ndash140 2012
[136] C-CHu J-T Lin F-J Lu F-P Chou andD-J Yang ldquoDetermi-nation of carotenoids in Dunaliella salina cultivated in Taiwanand antioxidant capacity of the algal carotenoid extractrdquo FoodChemistry vol 109 no 2 pp 439ndash446 2008
are indicated for the treatment or prevention of severalchronic diseases [77]
The antioxidant potential of carotenoid pigments andtheir ability to prevent cancer aging atherosclerosis coro-nary heart disease and degenerative diseases have beendescribed 120573-Carotene has higher provitamin A activitywhich is essential for vision and the correct functioning ofthe immune system Astaxanthin is linked to many healthbenefits such as protection against lipid peroxidation age-related macular degeneration reduced atherosclerosis andan increased immune response [102]
Fucoxanthin is considered as a promising dietary andweight loss supplement and for the treatment of obesityClinical studies by Abidov et al [127] demonstrated the effectof ldquoxanthigenrdquo a fucoxanthin based antiobesity supplementFurthermore fucoxanthinmay be useful for the prevention ofbone diseases such as osteoporosis and rheumatoid arthritisIt has also been reported to be effective for the therapeutictreatment of diabetic diseases suppressing insulin and hyper-glycemia [77]
Microalgae proteins are of great interest as a source ofbioactive peptides due to their therapeutic potential in thetreatment of various diseases [7] Proteins peptides andamino acids have functions that contribute to health benefitsThese compounds can include growth factors hormones andimmunomodulators and can help to replace damaged tissuesin addition to providing nutritional benefits Microalgaesuch as Chlorella and Spirulina (Arthrospira) may be usedas nutraceuticals or included in functional foods to preventdiseases and damage to cells and tissues due to their richprotein content and amino acid profile [102]
The antimicrobial action of certain enzymes (eglysozyme) and immunoglobulins has been reported andrecommended for people with different diseases (egCrohnrsquos disease) due to the existence of formulations withpeptides and free amino acids Studies of the healtheffects of lysozyme have been reported in the microalgaeSpirulina platensis [128] Chlorella [129] and Dunaliellasalina [130] Spirulina (Arthrospira) and Chlorella biomasspills are marketed as is ldquoHawaiian Spirulina Pacificardquo(httpspirulinagreennutritionalscomau) Other proteinscan also increase the production of cholecystokinin involvedin appetite suppression and the reduction of LDL-cholesterolProtein peptides from Chlorella have a potential as dietarysupplements for the prevention of oxidative stress-relateddiseases such as atherosclerosis coronary heart disease andcancer [39]
The essential fatty acids 120596-3 and 120596-6 in particular areimportant for the integrity of tissues 120574-Linolenic acid hastherapeutic applications in cosmetics to revitalize the skinand thus slow aging Linoleic and linolenic acids are essentialnutrients for the immune system and other related tissueregeneration processes Linoleic acid is also used for thetreatment of hyperplasia of the skin [102]
The most studied microalgal lipid compounds are thepolyunsaturated fatty acids (PUFAs) docosahexaenoic acid(120596-3 C226) (DHA) eicosapentaenoic acid (C20 120596-35)(EPA) and arachidonic acid (120596-6 C204) (ARA) Studies haveshown that dietary120596-3 PUFAs have a protective effect against
atherosclerotic heart disease [131] DHA and EPA showed theability to reduce problems associated with strokes and arthri-tis besides reducing hypertension lipid content (a decreasein triglycerides and an increase of HDL) and acting asanti-inflammatory agents DHA is also important in thedevelopment and function of the nervous system Further-more ARA and EPA are platelet aggregators vasoconstric-tors and vasodilators and have antiaggregative action on theendothelium as well as chemostatic activity in neutrophils[102]
Other lipid compounds with interesting bioactive prop-erties are the microalgal sterols Phytosterols have demon-strated reduction of total cholesterol (LDL) in humans byinhibiting its absorption from the intestine [50] Polysac-charides can be considered as dietary fibers associatedwith different physiological effects Insoluble fiber (cellulosehemicellulose and lignin) mainly promotes the movementof material through the digestive system thereby improvinglaxation and increasing satietyThey can also be considered asprebiotics because they promote the growth of gutmicrofloraincluding probiotic species Soluble fiber (oligosaccharidespectins and 120573-glucans) may reduce cholesterol and regulateblood glucose [7 132]
6 Conclusion
The proven ability of microalgae to produce bioactive com-pounds places these microorganisms in the biotechnologicalspotlight for applications in various areas of study especiallyin the life sciencesThe production ofmicroalgal metaboliteswhich stimulate defense mechanisms in the human bodyhas spurred intense study of the application of microalgalbiomass in various foods and pharmacological and medicalproducts There is obviously a need for further study of theidentified compounds and their activities in the treatmentand prevention of various diseases in addition to an ongoingsearch for other as yet undetected metabolites
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgment
The authors thank the National Counsel of Technologicaland Scientific Development (CNPq) for the Productivityin Technological Development and Innovative ExtensionScholarship
References
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[2] A A El Gamal ldquoBiological importance of marine algaerdquo SaudiPharmaceutical Journal vol 18 no 1 pp 1ndash25 2010
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[7] E Ibanez and A Cifuentes ldquoBenefits of using algae as naturalsources of functional ingredientsrdquo Journal of the Science of Foodand Agriculture vol 93 no 4 pp 703ndash709 2013
[8] G Markou and E Nerantzis ldquoMicroalgae for high-valuecompounds and biofuels production a review with focus oncultivation under stress conditionsrdquo Biotechnology Advancesvol 31 no 8 pp 1532ndash1542 2013
[9] R Harun M Singh G M Forde andM K Danquah ldquoBiopro-cess engineering ofmicroalgae to produce a variety of consumerproductsrdquo Renewable and Sustainable Energy Reviews vol 14no 3 pp 1037ndash1047 2010
[10] C Kolympiris N Kalaitzandonakes and D Miller ldquoPublicfunds and local biotechnology firm creationrdquo Research Policyvol 43 no 1 pp 121ndash137 2014
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extraction of 120574-linolenic acid and other lipids from Arthrospira(Spirulina)maxima comparison with organic solvent extrac-tionrdquo Food Chemistry vol 99 no 1 pp 57ndash63 2006
[21] I Romano M R Bellitti B Nicolaus et al ldquoLipid profilea useful chemotaxonomic marker for classification of a newcyanobacterium in Spirulina genusrdquo Phytochemistry vol 54 no3 pp 289ndash294 2000
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[30] L M Colla A L Muccillo-Baisch and J A Vieira CostaldquoSpirulina platensis effects on the levels of total cholesterol HDLand triacylglycerols in rabbits fed with a hypercholesterolemicdietrdquo Brazilian Archives of Biology and Technology vol 51 no 2pp 405ndash411 2008
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[39] M Plaza M Herrero A Alejandro Cifuentes and E IbanezldquoInnovative natural functional ingredients from microalgaerdquoJournal of Agricultural and Food Chemistry vol 57 no 16 pp7159ndash7170 2009
[40] J A V Costa E M Radmann V S Cerqueira G C Santosand M N Calheiros ldquoPerfil de acidos graxos das microalgasChlorella vulgaris e Chlorella minutissima cultivadas em difer-entes condicoesrdquo Alimentos e Nutricao Araraquara vol 17 no4 pp 429ndash436 2006
[41] K H Cha S W Kang C Y Kim B H Um Y R Naand C-H Pan ldquoEffect of pressurized liquids on extraction ofantioxidants from chlorella vulgarisrdquo Journal of Agricultural andFood Chemistry vol 58 no 8 pp 4756ndash4761 2010
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[45] L Zhao and B V Sweet ldquoLutein and zeaxanthin for maculardegenerationrdquo The American Journal of Health-System Phar-macy vol 65 no 13 pp 1232ndash1238 2008
[46] P Spolaore C Joannis-Cassan E Duran and A IsambertldquoCommercial applications of microalgaerdquo Journal of Bioscienceand Bioengineering vol 101 no 2 pp 87ndash96 2006
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[49] A Hosseini Tafreshi and M Shariati ldquoDunaliella biotechnol-ogy methods and applicationsrdquo Journal of Applied Microbiol-ogy vol 107 no 1 pp 14ndash35 2009
[50] M Francavilla P Trotta and R Luque ldquoPhytosterols fromDunaliella tertiolecta and Dunaliella salina a potentially novelindustrial applicationrdquo Bioresource Technology vol 101 no 11pp 4144ndash4150 2010
[51] F F Madkour and M M Abdel-Daim ldquoHepatoprotective andantioxidant activity of dunaliella salina in paracetamol-inducedacute toxicity in ratsrdquo Indian Journal of Pharmaceutical Sciencesvol 75 no 6 pp 642ndash648 2013
[52] T Chang S Ohta N Ikegami H Miyata T Kashimoto andM Kondo ldquoAntibiotic substances produced by a marine greenalgaDunaliella primolectardquo Bioresource Technology vol 44 no2 pp 149ndash153 1993
[53] M Herrero L Jaime P J Martın-Alvarez A Cifuentes and EIbanez ldquoOptimization of the extraction of antioxidants fromDunaliella salina microalga by pressurized liquidsrdquo Journal ofAgricultural and Food Chemistry vol 54 no 15 pp 5597ndash56032006
[54] R Leon M Martın J Vigara C Vilchez and J MVega ldquoMicroalgae mediated photoproduction of 120573-carotene inaqueous-organic two phase systemsrdquo Biomolecular Engineeringvol 20 no 4ndash6 pp 177ndash182 2003
[55] M Garcıa-Gonzalez J Moreno J C Manzano F J Florencioand M G Guerrero ldquoProduction of Dunaliella salina biomassrich in 9-119888119894119904-120573-carotene and lutein in a closed tubular photo-bioreactorrdquo Journal of Biotechnology vol 115 no 1 pp 81ndash902005
[56] D M M Kleinegris M Janssen W A Brandenburg andR H Wijffels ldquoContinuous production of carotenoids fromDunaliella salinardquo Enzyme and Microbial Technology vol 48no 3 pp 253ndash259 2011
[57] P Stolz and B Obermayer ldquoManufacturing microalgae for skincarerdquo Cosmetics amp Toiletries Science Applied vol 120 pp 99ndash106 2005
[58] M N Noaman ldquoEffect of potassium and nitrogen fertilizers onthe growth and biomass of some halophytes grown under highlevels of salinityrdquo Journal of Agronomy vol 3 no 1 pp 25ndash302004
[59] S O Lourenco Cultivo de Microalgas Marinhas Princıpios eAplicacoes RiMa Sao Paulo Brazil 2006
[60] G E Fogg ldquoThe ecological significance of extracellular prod-ucts of phytoplankton photosynthesisrdquo Botanica Marina vol26 no 1 pp 3ndash14 1983
[61] D L Nelson and M M Cox Princıpios de Bioquımica SarvierSao Paulo Brazil 4th edition 2004
[62] T Chrismadha andM A Borowitzka ldquoEffect of cell density andirradiance on growth proximate composition and eicosapen-taenoic acid production of Phaeodactylum tricornutum grownin a tubular photobioreactorrdquo Journal of Applied Phycology vol6 no 1 pp 67ndash74 1994
[63] A C Guedes L A Meireles H M Amaro and F X MalcataldquoChanges in lipid class and fatty acid composition of culturesof Pavlova lutheri in response to light intensityrdquo Journal of theAmerican Oil Chemistsrsquo Society vol 87 no 7 pp 791ndash801 2010
[64] H K Madhyastha S Sivashankari and T M Vatsala ldquoC-phycocyanin from Spirulina fussiformis exposed to blue lightdemonstrates higher efficacy of in vitro antioxidant activityrdquoBiochemical Engineering Journal vol 43 no 2 pp 221ndash2242009
[65] A Vonshak Spirulina platensis (Athrospira) Physiology Cell-Biology and Biotechnoloby Taylor amp Francis London UK 1997
[66] R D Fox Spirulina Production amp Potential Edisud ParisFrance 1996
BioMed Research International 13
[67] C U Ugwu H Aoyagi and H Uchiyama ldquoPhotobioreactorsfor mass cultivation of algaerdquo Bioresource Technology vol 99no 10 pp 4021ndash4028 2008
[68] S V Mohan M V Rohit P Chiranjeevi R Chandra and BNavaneeth ldquoHeterotrophic microalgae cultivation to synergizebiodiesel production with waste remediation progress andperspectivesrdquo Bioresource Technology 2014
[69] M G Morais and J A C Costa ldquoAn open pond system formicroalgal cultivationinrdquo in Biofuels from Algae A Pandey D-J Lee Y Chisti and C R Soccol Eds p 1 Elsevier 2014
[70] R E Lee Phycology Cambridge University Press New YorkNY USA 1980
[71] A RichmondHandbook ofMicroalgalMass Culture CRCPressBoston Mass USA 1990
[72] M Coca V M Barrocal S Lucas G Gonzalez-Benito andM T Garcıa-Cubero ldquoProtein production in Spirulina platensisbiomass using beet vinasse-supplemented culture mediardquo Foodand Bioproducts Processing 2014
[73] P-F Ip and F Chen ldquoPeroxynitrite and nitryl chloride enhanceastaxanthin production by the green microalga Chlorella zofin-giensis in heterotrophic culturerdquo Process Biochemistry vol 40no 11 pp 3595ndash3599 2005
[74] D L Alonso E-H Belarbi J M Fernandez-Sevilla JRodrıguez-Ruiz and E M Grima ldquoAcyl lipid compositionvariation related to culture age and nitrogen concentration incontinuous culture of the microalga Phaeodactylum tricornu-tumrdquo Phytochemistry vol 54 no 5 pp 461ndash471 2000
[75] W Schmidell A U Lima E Aquarone and W BorzaniBiotecnologia Industrial Volume 2 Edgard Blucher Sao PauloBrazil 2001
[76] R R L Guillard ldquoCulture of phytoplankton for feeding marineinvertebratesrdquo in Culture of Marine Invertebrate Animals W LSmith and M H Chanley Eds pp 29ndash60 Plenum New YorkNY USA 1975
[77] R Pangestuti and S-K Kim ldquoBiological activities and healthbenefit effects of natural pigments derived from marine algaerdquoJournal of Functional Foods vol 3 no 4 pp 255ndash266 2011
[78] K Skjanes C Rebours and P Lindblad ldquoPotential for greenmicroalgae to produce hydrogen pharmaceuticals and otherhigh value products in a combined processrdquo Critical Reviews inBiotechnology vol 33 no 2 pp 172ndash215 2013
[79] I Rodrıguez-Meizoso L Jaime S Santoyo F J Senorans ACifuentes and E Ibanez ldquoSubcritical water extraction andcharacterization of bioactive compounds from Haematococcuspluvialis microalgardquo Journal of Pharmaceutical and BiomedicalAnalysis vol 51 no 2 pp 456ndash463 2010
[80] M Herrero M Castro-Puyana J A Mendiola and E IbanezldquoCompressed fluids for the extraction of bioactive compoundsrdquoTrends in Analytical Chemistry vol 43 pp 67ndash83 2013
[81] N K Singh and D W Dhar ldquoMicroalgae as second generationbiofuel A reviewrdquo Agronomy for Sustainable Development vol31 no 4 pp 605ndash629 2011
[82] L Brennan and P Owende ldquoBiofuels frommicroalgae towardsmeeting advanced fuel standardsrdquo in Advanced Biofuels andBioproducts JW Lee Ed pp 553ndash599 Springer NewYork NYUSA 2013
[83] A Singh P S Nigam and J D Murphy ldquoRenewable fuels fromalgae an answer to debatable land based fuelsrdquo BioresourceTechnology vol 102 no 1 pp 10ndash16 2011
[84] P Perez-Lopez S Gonzalez-Garcıa R G Ulloa J SineiroG Feijoo and M T Moreira ldquoLife cycle assessment of the
production of bioactive compounds from Tetraselmis suecica atpilot scalerdquo Journal of Cleaner Production vol 64 pp 323ndash3312014
[85] B Subhadra ldquoAlgal biorefinery-based industry an approachto address fuel and food insecurity for a carbon-smart worldrdquoJournal of the Science of Food and Agriculture vol 91 no 1 pp2ndash13 2011
[86] D J Newman and G M Cragg ldquoNatural products as sourcesof new drugs over the 30 years from 1981 to 2010rdquo Journal ofNatural Products vol 75 no 3 pp 311ndash335 2012
[87] H-B Li K-W Cheng C-C Wong K-W Fan F Chen andY Jiang ldquoEvaluation of antioxidant capacity and total phenoliccontent of different fractions of selected microalgaerdquo FoodChemistry vol 102 no 3 pp 771ndash776 2007
[88] T M Mata A A Martins and N S Caetano ldquoMicroalgaefor biodiesel production and other applications a reviewrdquoRenewable and Sustainable EnergyReviews vol 14 no 1 pp 217ndash232 2010
[89] A Gupta and J K Sainis ldquoIsolation of C-phycocyanin fromSynechococcus sp (Anacystis nidulans BD1)rdquo Journal of AppliedPhycology vol 22 no 3 pp 231ndash233 2010
[90] P J Viskari and C L Colyer ldquoRapid extraction of phyco-biliproteins from cultured cyanobacteria samplesrdquo AnalyticalBiochemistry vol 319 no 2 pp 263ndash271 2003
[91] R Bermejo Roman J M Alvarez-Pez F G Acien Fernandezand E Molina Grima ldquoRecovery of pure B-phycoerythrin fromthe microalga Porphyridium cruentumrdquo Journal of Biotechnol-ogy vol 93 no 1 pp 73ndash85 2002
[92] C I Cazzonelli ldquoCarotenoids in nature insights from plantsand beyondrdquo Functional Plant Biology vol 38 no 11 pp 833ndash847 2011
[93] M A Hejazi and R HWijffels ldquoMilking of microalgaerdquo Trendsin Biotechnology vol 22 no 4 pp 189ndash194 2004
[94] S Arad and O Levy-Ontman ldquoRed microalgal cell-wallpolysaccharides biotechnological aspectsrdquo Current Opinion inBiotechnology vol 21 no 3 pp 358ndash364 2010
[95] M Kim J H Yim S-Y Kim et al ldquoIn vitro inhibitionof influenza A virus infection by marine microalga-derivedsulfated polysaccharide p-KG03rdquoAntiviral Research vol 93 no2 pp 253ndash259 2012
[96] Z A Mohamed ldquoPolysaccharides as a protective responseagainst microcystin-induced oxidative stress in Chlorella vul-garis and Scenedesmus quadricauda and their possible signifi-cance in the aquatic ecosystemrdquo Ecotoxicology vol 17 no 6 pp504ndash516 2008
[97] T Tannin-Spitz M Bergman D Van-Moppes S Grossmanand S Arad ldquoAntioxidant activity of the polysaccharide of thered microalga Porphyridium sprdquo Journal of Applied Phycologyvol 17 no 3 pp 215ndash222 2005
[98] J W Prakash M Johnson and S Jeeva ldquoAntimicrobial activityof certain fresh water microalgae from Thamirabarani RiverTamil Nadu South Indiardquo Asian Pacific Journal of TropicalBiomedicine vol 1 supplement no 2 pp S170ndashS173 2011
[99] H M Amaro A C Guedes and F X Malcata ldquoAntimicrobialactivities of microalgae an invited reviewrdquo in Science againstMicrobial Pathogens Communicating Current Research andTechnological Advances A Mendez-Vilas Ed pp 1272ndash12802011
[100] V J Smith A PDesbois and E ADyrynda ldquoConventional andunconventional antimicrobials from fish marine invertebratesand micro-algaerdquo Marine Drugs vol 8 no 4 pp 1213ndash12622010
14 BioMed Research International
[101] M F D J Raposo A M M B de Morais and R M SC de Morais ldquoInfluence of sulphate on the composition andantibacterial and antiviral properties of the exopolysaccharidefrom Porphyridium cruentumrdquo Life Sciences vol 101 no 1-2 pp56ndash63 2014
[102] M F De Jesus Raposo R M S C De Morais and A M M BDe Morais ldquoHealth applications of bioactive compounds frommarine microalgaerdquo Life Sciences vol 93 no 15 pp 479ndash4862013
[103] A Smelcerovic Z Knezevic-Jugovic and Z PetronijevicldquoMicrobial polysaccharides and their derivatives as current andprospective pharmaceuticalsrdquo Current Pharmaceutical Designvol 14 no 29 pp 3168ndash3195 2008
[104] M T Madigan J M Martinko P V Dunlap and D P ClarkMicrobiologia de Brock Artmed Editora 12th edition 2010
[105] M G de Morais J A V Costa P H L Pranke et alldquoDevelopment of a newnanofiber scaffold for usewith stemcellsin a third degree burn animal modelrdquo Burns Oxford vol 40 no8 pp 1650ndash1660 2014
[106] M G de Morais C Stillings R Dersch et al ldquoPreparation ofnanofibers containing the microalga Spirulina (Arthrospira)rdquoBioresource Technology vol 101 no 8 pp 2872ndash2876 2010
[107] D Steffens M Lersch A Rosa et al ldquoA new biomaterialof nanofibers with the microalga Spirulina as scaffolds tocultivate with stem cells for use in tissue engineeringrdquo Journalof Biomedical Nanotechnology vol 9 no 4 pp 710ndash718 2013
[108] C Barrow and F ShahidiMarine Nutraceuticals and FunctionalFoods CRC Press Taylor amp Francis Boca Raton Fla USA2008
[109] M N A Khan J-Y ChoM-C Lee et al ldquoIsolation of two anti-inflammatory and one pro-inflammatory polyunsaturated fattyacids from the brown seaweed Undaria pinnatifidardquo Journal ofAgricultural and Food Chemistry vol 55 no 17 pp 6984ndash69882007
[110] M S Matsui N Muizzuddin S Arad and K MarenusldquoSulfated polysaccharides from redmicroalgae have antiinflam-matory properties in vitro and in vivordquo Applied Biochemistryand Biotechnology vol 104 no 1 pp 13ndash22 2003
[111] V B Bhat and K M Madyastha ldquoScavenging of peroxynitriteby phycocyanin and phycocyanobilin from Spirulina platensisprotection against oxidative damage to DNArdquo Biochemical andBiophysical Research Communications vol 285 no 2 pp 262ndash266 2001
[112] I A Schepetkin and M T Quinn ldquoBotanical polysaccharidesmacrophage immunomodulation and therapeutic potentialrdquoInternational Immunopharmacology vol 6 no 3 pp 317ndash3332006
[113] J K Park Z-H Kim C G Lee et al ldquoCharacterization andimmunostimulating activity of a water-soluble polysaccharideisolated from Haematococcus lacustrisrdquo Biotechnology and Bio-process Engineering vol 16 no 6 pp 1090ndash1098 2011
[114] S Guzman A Gato M Lamela M Freire-Garabal and J MCalleja ldquoAnti-inflammatory and immunomodulatory activitiesof polysaccharide from Chlorella stigmatophora and Phaeo-dactylum tricornutumrdquo Phytotherapy Research vol 17 no 6 pp665ndash670 2003
[115] E Ryckebosch C Bruneel R Termote-Verhalle K Goiris KMuylaert and I Foubert ldquoNutritional evaluation of microalgaeoils rich in omega-3 long chain polyunsaturated fatty acids as analternative for fish oilrdquo Food Chemistry vol 160 pp 393ndash4002014
[116] P Zhao Z Zang X Xie A Huang and G Wang ldquoTheinfluence of different flocculants on the physiological activityand fucoxanthin production of Phaeodactylum tricornutumrdquoProcess Biochemistry vol 49 no 4 pp 681ndash687 2014
[117] D Moreau C Tomasoni C Jacquot et al ldquoCultivated microal-gae and the carotenoid fucoxanthin from Odontella auritaas potent anti-proliferative agents in bronchopulmonary andepithelial cell linesrdquo Environmental Toxicology and Pharmacol-ogy vol 22 no 1 pp 97ndash103 2006
[118] H Maeda M Hosokawa T Sashima K Funayama and KMiyashita ldquoFucoxanthin from edible seaweed Undaria pinnati-fida shows antiobesity effect through UCP1 expression in whiteadipose tissuesrdquo Biochemical and Biophysical Research Commu-nications vol 332 no 2 pp 392ndash397 2005
[119] J E Piero Estrada P Bermejo Bescos and A M Villar delFresno ldquoAntioxidant activity of different fractions of Spirulinaplatensis protean extractrdquo IL Farmaco vol 56 no 5ndash7 pp 497ndash500 2001
[120] S-M Kang S-J Heo K-N Kim S-H Lee and Y-JJeon ldquoIsolation and identification of new compound 2710158401015840-phloroglucinol-661015840-bieckol from brown algae Ecklonia cavaand its antioxidant effectrdquo Journal of Functional Foods vol 4no 1 pp 158ndash166 2012
[121] HHAbdEl-Baky F K El Baz andG S El-Baroty ldquoProductionof phenolic compounds from Spirulinamaximamicroalgae andits protective effectsrdquoAfrican Journal of Biotechnology vol 8 no24 pp 7059ndash7067 2009
[122] A C Guedes H M Amaro and F X Malcata ldquoMicroalgae assources of carotenoidsrdquoMarineDrugs vol 9 no 4 pp 625ndash6442011
[123] G L Renju G M Kurup and K C H Saritha ldquoEffect oflycopene from Chlorella marina on high cholesterol-inducedoxidative damage and inflammation in ratsrdquo Inflammopharma-cology vol 22 no 1 pp 45ndash54 2014
[124] G L Renju G M Kurup and C H S Kumari ldquoAnti-inflammatory activity of lycopene isolated from Chlorellamarina onType II Collagen induced arthritis in SpragueDawleyratsrdquo Immunopharmacology and Immunotoxicology vol 35 no2 pp 282ndash291 2013
[125] C Vılchez E Forjan M Cuaresma F Bedmar I Garbayo andJ M Vega ldquoMarine carotenoids biological functions andcommercial applicationsrdquo Marine Drugs vol 9 no 3 pp 319ndash333 2011
[126] G Richardson ldquoBeyond eye healthrdquo Life Extension Magazine2011 httpwwwleforgMagazine20117Beyond-Eye-HealthPage-01
[127] M Abidov Z Ramazanov R Seifulla and S Grachev ldquoTheeffects of Xanthigen in the weight management of obesepremenopausal women with non-alcoholic fatty liver diseaseand normal liver fatrdquo Diabetes Obesity and Metabolism vol 12no 1 pp 72ndash81 2010
[128] H M Ragap R H Khalil and H HMutawie ldquoImmunostimu-lant effects of dietary Spirulina platensis on tilapia Oreochromisniloticusrdquo Journal of Applied Pharmaceutical Science vol 2 no2 pp 26ndash31 2012
[129] W Xu Z Gao Z Qi M Qiu J-Q Peng and R Shao ldquoEffect ofdietary chlorella on the growth performance and physiologicalparameters of gibel carp Carassius auratus gibeliordquo TurkishJournal of Fisheries and Aquatic Sciences vol 14 no 1 pp 53ndash572014
[130] P Amaninejad H Emadi M Ematiazjoo et al ldquoEffects ofDunaliella microalgae (Dunaliella salina) on different level of
BioMed Research International 15
IgM Immunoglobulin in rainbow trout (Oncrohynchusmykiss)rdquoGlobal Journal of Biodiversity Science and Management vol 3no 2 pp 237ndash242 2013
[131] V Mimouni L Ulmann V Pasquet et al ldquoThe potential ofmicroalgae for the production of bioactive molecules of phar-maceutical interestrdquoCurrent Pharmaceutical Biotechnology vol13 no 15 pp 2733ndash2750 2012
[132] S M Tosh and S Yada ldquoDietary fibres in pulse seeds and frac-tions characterization functional attributes and applicationsrdquoFood Research International vol 43 no 2 pp 450ndash460 2010
[133] H M Amaro R Barros A C Guedes I Sousa-Pinto and FXMalcata ldquoMicroalgal compoundsmodulate carcinogenesis inthe gastrointestinal tractrdquo Trends in Biotechnology vol 31 no 2pp 92ndash98 2013
[134] S S M Mostafa ldquoMicroalgal biotechnology prospects andapplicationsrdquo in Plant Science chapter 12 pp 275ndash314 InTech2012
[135] L Custodio T Justo L Silvestre et al ldquoMicroalgae of dif-ferent phyla display antioxidant metal chelating and acetyl-cholinesterase inhibitory activitiesrdquoFoodChemistry vol 131 no1 pp 134ndash140 2012
[136] C-CHu J-T Lin F-J Lu F-P Chou andD-J Yang ldquoDetermi-nation of carotenoids in Dunaliella salina cultivated in Taiwanand antioxidant capacity of the algal carotenoid extractrdquo FoodChemistry vol 109 no 2 pp 439ndash446 2008
[3] I Moreno-Garrido ldquoMicroalgae immobilization current tech-niques and usesrdquo Bioresource Technology vol 99 no 10 pp3949ndash3964 2008
[4] R-B Volk and F H Furkert ldquoAntialgal antibacterial andantifungal activity of two metabolites produced and excretedby cyanobacteria during growthrdquoMicrobiological Research vol161 no 2 pp 180ndash186 2006
[5] R-B Volk ldquoA newly developed assay for the quantitativedetermination of antimicrobial (anticyanobacterial) activity ofboth hydrophilic and lipophilic test compounds without anyrestrictionrdquoMicrobiological Research vol 163 no 2 pp 161ndash1672008
[6] D F Smee K W Bailey M-H Wong et al ldquoTreatment ofinfluenza A (H1N1) virus infections in mice and ferrets withcyanovirin-Nrdquo Antiviral Research vol 80 no 3 pp 266ndash2712008
[7] E Ibanez and A Cifuentes ldquoBenefits of using algae as naturalsources of functional ingredientsrdquo Journal of the Science of Foodand Agriculture vol 93 no 4 pp 703ndash709 2013
[8] G Markou and E Nerantzis ldquoMicroalgae for high-valuecompounds and biofuels production a review with focus oncultivation under stress conditionsrdquo Biotechnology Advancesvol 31 no 8 pp 1532ndash1542 2013
[9] R Harun M Singh G M Forde andM K Danquah ldquoBiopro-cess engineering ofmicroalgae to produce a variety of consumerproductsrdquo Renewable and Sustainable Energy Reviews vol 14no 3 pp 1037ndash1047 2010
[10] C Kolympiris N Kalaitzandonakes and D Miller ldquoPublicfunds and local biotechnology firm creationrdquo Research Policyvol 43 no 1 pp 121ndash137 2014
[11] S Bhagavathy P Sumathi and I Jancy Sherene Bell ldquoGreenalgae Chlorococcum humicola-a new source of bioactive com-pounds with antimicrobial activityrdquo Asian Pacific Journal ofTropical Biomedicine vol 1 no 1 pp S1ndashS7 2011
[12] A M F Palavra J P Coelho J G Barroso et al ldquoSupercrit-ical carbon dioxide extraction of bioactive compounds frommicroalgae and volatile oils from aromatic plantsrdquo Journal ofSupercritical Fluids vol 60 pp 21ndash27 2011
[13] I Priyadarshani and B Rath ldquoCommercial and industrialapplications of micro algaemdasha reviewrdquo Journal of Algal BiomassUtilization vol 3 no 4 pp 89ndash100 2012
[14] JW Blunt B R CoppM H GMunro P T Northcote andMR Prinsep ldquoMarine natural productsrdquoNatural Product Reportsvol 23 no 1 pp 26ndash78 2006
[15] A M S Mayer and M T Hamann ldquoMarine pharmacologyin 2001-2002 marine compounds with anthelmintic antibacte-rial anticoagulant antidiabetic antifungal anti-inflammatoryantimalarial antiplatelet antiprotozoal antituberculosis andantiviral activities affecting the cardiovascular immune andnervous systems and other miscellaneous mechanisms ofactionrdquo Comparative Biochemistry and Physiology Part C Toxi-cology amp Pharmacology vol 140 no 3-4 pp 265ndash286 2005
[16] M Plaza S Santoyo L Jaime et al ldquoScreening for bioactivecompounds from algaerdquo Journal of Pharmaceutical and Biomed-ical Analysis vol 51 no 2 pp 450ndash455 2010
[17] I Rodrıguez-Meizoso L Jaime S Santoyo et al ldquoPressurizedfluid extraction of bioactive compounds from Phormidiumspeciesrdquo Journal of Agricultural and Food Chemistry vol 56 no10 pp 3517ndash3523 2008
[18] L R Carvalho A Costa-Neves G A A Conserva et alldquoBiologically active compounds from cyano bacteria extracts in
vivo and in vitro aspectsrdquo Brazilian Journal of Pharmacognosyvol 23 no 3 pp 471ndash480 2013
[19] B Nobre FMarcelo R Passos et al ldquoSupercritical carbon diox-ide extraction of astaxanthin and other carotenoids from themicroalga Haematococcus pluvialisrdquo European Food Researchand Technology vol 223 no 6 pp 787ndash790 2006
[20] R L Mendes A D Reis and A F Palavra ldquoSupercritical CO2
extraction of 120574-linolenic acid and other lipids from Arthrospira(Spirulina)maxima comparison with organic solvent extrac-tionrdquo Food Chemistry vol 99 no 1 pp 57ndash63 2006
[21] I Romano M R Bellitti B Nicolaus et al ldquoLipid profilea useful chemotaxonomic marker for classification of a newcyanobacterium in Spirulina genusrdquo Phytochemistry vol 54 no3 pp 289ndash294 2000
[22] J A C Costa and M G Morais ldquoMicroalgae for food produc-tionrdquo in Fermentation Process Engineering in the Food IndustryC R Soccol A Pandey and C Larroche Eds p 486 Taylor ampFrancis 2013
[23] MAAmbrosi CO Reinehr T E Bertolin et al ldquoPropriedadesde saude de Spirulina spprdquo Revista de Ciencias FarmaceuticasBasica e Aplicada vol 29 no 2 pp 109ndash117 2008
[24] J A Borges G M Rosa L H R Meza A A Henrard M RA Z Souza and J A V Costa ldquoSpirulina sp LEB-18 cultureusing effluent from the anaerobic digestionrdquo Brazilian Journalof Chemical Engineering vol 30 no 2 pp 277ndash287 2013
[25] F S Antelo J A V Costa and S J Kalil ldquoThermal degradationkinetics of the phycocyanin from Spirulina platensisrdquo Biochem-ical Engineering Journal vol 41 no 1 pp 43ndash47 2008
[26] S T Silveira J F M Burkert J A V Costa C A V Burkertand S J Kalil ldquoOptimization of phycocyanin extraction fromSpirulina platensis using factorial designrdquo Bioresource Technol-ogy vol 98 no 8 pp 1629ndash1634 2007
[27] L M Colla C O Reinehr C Reichert and J A V Costa ldquoPro-duction of biomass and nutraceutical compounds by Spirulinaplatensis under different temperature and nitrogen regimesrdquoBioresource Technology vol 98 no 7 pp 1489ndash1493 2007
[28] R P Rastogi and R P Sinha ldquoBiotechnological and industrialsignificance of cyanobacterial secondary metabolitesrdquo Biotech-nology Advances vol 27 no 4 pp 521ndash539 2009
[29] N A E Semary ldquoThe characterisation of bioactive compoundsfrom an Egyptian Leptolyngbya sp strainrdquo Annals of Microbiol-ogy vol 62 no 1 pp 55ndash59 2012
[30] L M Colla A L Muccillo-Baisch and J A Vieira CostaldquoSpirulina platensis effects on the levels of total cholesterol HDLand triacylglycerols in rabbits fed with a hypercholesterolemicdietrdquo Brazilian Archives of Biology and Technology vol 51 no 2pp 405ndash411 2008
[31] P V Torres-Duran A Ferreira-Hermosillo and M A Juarez-Oropeza ldquoAntihyperlipemic and antihypertensive effects ofSpirulina maxima in an open sample of Mexican population apreliminary reportrdquo Lipids in Health and Disease vol 6 article33 2007
[32] S AnshumanMDeepikaG Sharmila andCMuthukumaranldquoEffect of glucose and phytohaemagglutinin (PHA) richPhaseo-lus vulgaris extract on growth and protein synthesis of pharma-ceutically important cyanobacteriaNostoc ellipsosporumNCIM2786rdquo Journal of Genetic Engineering and Biotechnology vol 11no 1 pp 33ndash37 2013
[33] IMaldener andAMMuro-PasterEncyclopedia of Life Sciences(ELS) John Wiley amp Sons Chichester UK 2010
12 BioMed Research International
[34] M Temina H Rezankova T Rezanka and V M DembitskyldquoDiversity of the fatty acids of the Nostoc species and theirstatistical analysisrdquoMicrobiological Research vol 162 no 4 pp308ndash321 2007
[35] Z Deng Q Hu F Lu G Liu and Z Hu ldquoColony developmentand physiological characterization of the edible blue-greenalga Nostoc sphaeroides (Nostocaceae Cyanophyta)rdquo Progressin Natural Science vol 18 no 12 pp 1475ndash1484 2008
[36] M R Boyd K R Gustafson J B McMahon et al ldquoDiscoveryof cyanovirin-N a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycopro-tein gp120 potential applications to microbicide developmentrdquoAntimicrobial Agents and Chemotherapy vol 41 no 7 pp 1521ndash1530 1997
[37] M Wang Y-N Xu G-Z Jiang L-B Li and T-Y KuangldquoMembrane lipids and their fatty acid composition in Nostocflagelliforme cellsrdquoActa Botanica Sinica vol 42 no 12 pp 1263ndash1266 2000
[38] J Masojıdek and O Prasil ldquoThe development of microalgalbiotechnology in the Czech Republicrdquo Journal of IndustrialMicrobiology amp Biotechnology vol 37 no 12 pp 1307ndash1317 2010
[39] M Plaza M Herrero A Alejandro Cifuentes and E IbanezldquoInnovative natural functional ingredients from microalgaerdquoJournal of Agricultural and Food Chemistry vol 57 no 16 pp7159ndash7170 2009
[40] J A V Costa E M Radmann V S Cerqueira G C Santosand M N Calheiros ldquoPerfil de acidos graxos das microalgasChlorella vulgaris e Chlorella minutissima cultivadas em difer-entes condicoesrdquo Alimentos e Nutricao Araraquara vol 17 no4 pp 429ndash436 2006
[41] K H Cha S W Kang C Y Kim B H Um Y R Naand C-H Pan ldquoEffect of pressurized liquids on extraction ofantioxidants from chlorella vulgarisrdquo Journal of Agricultural andFood Chemistry vol 58 no 8 pp 4756ndash4761 2010
[42] F Kokou P Makridis M Kentouri and P Divanach ldquoAntibac-terial activity inmicroalgae culturesrdquoAquaculture Research vol43 no 10 pp 1520ndash1527 2012
[43] L Li W Li Y-H Kim and YW Lee ldquoChlorella vulgaris extractameliorates carbon tetrachloride-induced acute hepatic injuryin micerdquo Experimental and Toxicologic Pathology vol 65 no 1-2 pp 73ndash80 2013
[44] N B Medina-Jaritz L F Carmona-Ugalde J C Lopez-CedilloandF S L Ruiloba-DeLeon ldquoAntibacterial activity ofmethano-lic extracts from Dunaliella salina and Chlorella vulgarisrdquo TheFASEB Journal vol 27 abstract 11675 2013
[45] L Zhao and B V Sweet ldquoLutein and zeaxanthin for maculardegenerationrdquo The American Journal of Health-System Phar-macy vol 65 no 13 pp 1232ndash1238 2008
[46] P Spolaore C Joannis-Cassan E Duran and A IsambertldquoCommercial applications of microalgaerdquo Journal of Bioscienceand Bioengineering vol 101 no 2 pp 87ndash96 2006
[47] C Rosch and C Posten ldquoChallenges and perspectives ofmicroalgae productionrdquo TechnikfolgenabschatzungmdashTheorieund Praxis vol 21 no 1 2012
[48] K Preetha L John C S Subin and K K Vijayan ldquoPhenotypicand genetic characterization of Dunaliella (Chlorophyta) fromIndian salinas and their diversityrdquoAquatic Biosystems vol 8 no1 article 27 2012
[49] A Hosseini Tafreshi and M Shariati ldquoDunaliella biotechnol-ogy methods and applicationsrdquo Journal of Applied Microbiol-ogy vol 107 no 1 pp 14ndash35 2009
[50] M Francavilla P Trotta and R Luque ldquoPhytosterols fromDunaliella tertiolecta and Dunaliella salina a potentially novelindustrial applicationrdquo Bioresource Technology vol 101 no 11pp 4144ndash4150 2010
[51] F F Madkour and M M Abdel-Daim ldquoHepatoprotective andantioxidant activity of dunaliella salina in paracetamol-inducedacute toxicity in ratsrdquo Indian Journal of Pharmaceutical Sciencesvol 75 no 6 pp 642ndash648 2013
[52] T Chang S Ohta N Ikegami H Miyata T Kashimoto andM Kondo ldquoAntibiotic substances produced by a marine greenalgaDunaliella primolectardquo Bioresource Technology vol 44 no2 pp 149ndash153 1993
[53] M Herrero L Jaime P J Martın-Alvarez A Cifuentes and EIbanez ldquoOptimization of the extraction of antioxidants fromDunaliella salina microalga by pressurized liquidsrdquo Journal ofAgricultural and Food Chemistry vol 54 no 15 pp 5597ndash56032006
[54] R Leon M Martın J Vigara C Vilchez and J MVega ldquoMicroalgae mediated photoproduction of 120573-carotene inaqueous-organic two phase systemsrdquo Biomolecular Engineeringvol 20 no 4ndash6 pp 177ndash182 2003
[55] M Garcıa-Gonzalez J Moreno J C Manzano F J Florencioand M G Guerrero ldquoProduction of Dunaliella salina biomassrich in 9-119888119894119904-120573-carotene and lutein in a closed tubular photo-bioreactorrdquo Journal of Biotechnology vol 115 no 1 pp 81ndash902005
[56] D M M Kleinegris M Janssen W A Brandenburg andR H Wijffels ldquoContinuous production of carotenoids fromDunaliella salinardquo Enzyme and Microbial Technology vol 48no 3 pp 253ndash259 2011
[57] P Stolz and B Obermayer ldquoManufacturing microalgae for skincarerdquo Cosmetics amp Toiletries Science Applied vol 120 pp 99ndash106 2005
[58] M N Noaman ldquoEffect of potassium and nitrogen fertilizers onthe growth and biomass of some halophytes grown under highlevels of salinityrdquo Journal of Agronomy vol 3 no 1 pp 25ndash302004
[59] S O Lourenco Cultivo de Microalgas Marinhas Princıpios eAplicacoes RiMa Sao Paulo Brazil 2006
[60] G E Fogg ldquoThe ecological significance of extracellular prod-ucts of phytoplankton photosynthesisrdquo Botanica Marina vol26 no 1 pp 3ndash14 1983
[61] D L Nelson and M M Cox Princıpios de Bioquımica SarvierSao Paulo Brazil 4th edition 2004
[62] T Chrismadha andM A Borowitzka ldquoEffect of cell density andirradiance on growth proximate composition and eicosapen-taenoic acid production of Phaeodactylum tricornutum grownin a tubular photobioreactorrdquo Journal of Applied Phycology vol6 no 1 pp 67ndash74 1994
[63] A C Guedes L A Meireles H M Amaro and F X MalcataldquoChanges in lipid class and fatty acid composition of culturesof Pavlova lutheri in response to light intensityrdquo Journal of theAmerican Oil Chemistsrsquo Society vol 87 no 7 pp 791ndash801 2010
[64] H K Madhyastha S Sivashankari and T M Vatsala ldquoC-phycocyanin from Spirulina fussiformis exposed to blue lightdemonstrates higher efficacy of in vitro antioxidant activityrdquoBiochemical Engineering Journal vol 43 no 2 pp 221ndash2242009
[65] A Vonshak Spirulina platensis (Athrospira) Physiology Cell-Biology and Biotechnoloby Taylor amp Francis London UK 1997
[66] R D Fox Spirulina Production amp Potential Edisud ParisFrance 1996
BioMed Research International 13
[67] C U Ugwu H Aoyagi and H Uchiyama ldquoPhotobioreactorsfor mass cultivation of algaerdquo Bioresource Technology vol 99no 10 pp 4021ndash4028 2008
[68] S V Mohan M V Rohit P Chiranjeevi R Chandra and BNavaneeth ldquoHeterotrophic microalgae cultivation to synergizebiodiesel production with waste remediation progress andperspectivesrdquo Bioresource Technology 2014
[69] M G Morais and J A C Costa ldquoAn open pond system formicroalgal cultivationinrdquo in Biofuels from Algae A Pandey D-J Lee Y Chisti and C R Soccol Eds p 1 Elsevier 2014
[70] R E Lee Phycology Cambridge University Press New YorkNY USA 1980
[71] A RichmondHandbook ofMicroalgalMass Culture CRCPressBoston Mass USA 1990
[72] M Coca V M Barrocal S Lucas G Gonzalez-Benito andM T Garcıa-Cubero ldquoProtein production in Spirulina platensisbiomass using beet vinasse-supplemented culture mediardquo Foodand Bioproducts Processing 2014
[73] P-F Ip and F Chen ldquoPeroxynitrite and nitryl chloride enhanceastaxanthin production by the green microalga Chlorella zofin-giensis in heterotrophic culturerdquo Process Biochemistry vol 40no 11 pp 3595ndash3599 2005
[74] D L Alonso E-H Belarbi J M Fernandez-Sevilla JRodrıguez-Ruiz and E M Grima ldquoAcyl lipid compositionvariation related to culture age and nitrogen concentration incontinuous culture of the microalga Phaeodactylum tricornu-tumrdquo Phytochemistry vol 54 no 5 pp 461ndash471 2000
[75] W Schmidell A U Lima E Aquarone and W BorzaniBiotecnologia Industrial Volume 2 Edgard Blucher Sao PauloBrazil 2001
[76] R R L Guillard ldquoCulture of phytoplankton for feeding marineinvertebratesrdquo in Culture of Marine Invertebrate Animals W LSmith and M H Chanley Eds pp 29ndash60 Plenum New YorkNY USA 1975
[77] R Pangestuti and S-K Kim ldquoBiological activities and healthbenefit effects of natural pigments derived from marine algaerdquoJournal of Functional Foods vol 3 no 4 pp 255ndash266 2011
[78] K Skjanes C Rebours and P Lindblad ldquoPotential for greenmicroalgae to produce hydrogen pharmaceuticals and otherhigh value products in a combined processrdquo Critical Reviews inBiotechnology vol 33 no 2 pp 172ndash215 2013
[79] I Rodrıguez-Meizoso L Jaime S Santoyo F J Senorans ACifuentes and E Ibanez ldquoSubcritical water extraction andcharacterization of bioactive compounds from Haematococcuspluvialis microalgardquo Journal of Pharmaceutical and BiomedicalAnalysis vol 51 no 2 pp 456ndash463 2010
[80] M Herrero M Castro-Puyana J A Mendiola and E IbanezldquoCompressed fluids for the extraction of bioactive compoundsrdquoTrends in Analytical Chemistry vol 43 pp 67ndash83 2013
[81] N K Singh and D W Dhar ldquoMicroalgae as second generationbiofuel A reviewrdquo Agronomy for Sustainable Development vol31 no 4 pp 605ndash629 2011
[82] L Brennan and P Owende ldquoBiofuels frommicroalgae towardsmeeting advanced fuel standardsrdquo in Advanced Biofuels andBioproducts JW Lee Ed pp 553ndash599 Springer NewYork NYUSA 2013
[83] A Singh P S Nigam and J D Murphy ldquoRenewable fuels fromalgae an answer to debatable land based fuelsrdquo BioresourceTechnology vol 102 no 1 pp 10ndash16 2011
[84] P Perez-Lopez S Gonzalez-Garcıa R G Ulloa J SineiroG Feijoo and M T Moreira ldquoLife cycle assessment of the
production of bioactive compounds from Tetraselmis suecica atpilot scalerdquo Journal of Cleaner Production vol 64 pp 323ndash3312014
[85] B Subhadra ldquoAlgal biorefinery-based industry an approachto address fuel and food insecurity for a carbon-smart worldrdquoJournal of the Science of Food and Agriculture vol 91 no 1 pp2ndash13 2011
[86] D J Newman and G M Cragg ldquoNatural products as sourcesof new drugs over the 30 years from 1981 to 2010rdquo Journal ofNatural Products vol 75 no 3 pp 311ndash335 2012
[87] H-B Li K-W Cheng C-C Wong K-W Fan F Chen andY Jiang ldquoEvaluation of antioxidant capacity and total phenoliccontent of different fractions of selected microalgaerdquo FoodChemistry vol 102 no 3 pp 771ndash776 2007
[88] T M Mata A A Martins and N S Caetano ldquoMicroalgaefor biodiesel production and other applications a reviewrdquoRenewable and Sustainable EnergyReviews vol 14 no 1 pp 217ndash232 2010
[89] A Gupta and J K Sainis ldquoIsolation of C-phycocyanin fromSynechococcus sp (Anacystis nidulans BD1)rdquo Journal of AppliedPhycology vol 22 no 3 pp 231ndash233 2010
[90] P J Viskari and C L Colyer ldquoRapid extraction of phyco-biliproteins from cultured cyanobacteria samplesrdquo AnalyticalBiochemistry vol 319 no 2 pp 263ndash271 2003
[91] R Bermejo Roman J M Alvarez-Pez F G Acien Fernandezand E Molina Grima ldquoRecovery of pure B-phycoerythrin fromthe microalga Porphyridium cruentumrdquo Journal of Biotechnol-ogy vol 93 no 1 pp 73ndash85 2002
[92] C I Cazzonelli ldquoCarotenoids in nature insights from plantsand beyondrdquo Functional Plant Biology vol 38 no 11 pp 833ndash847 2011
[93] M A Hejazi and R HWijffels ldquoMilking of microalgaerdquo Trendsin Biotechnology vol 22 no 4 pp 189ndash194 2004
[94] S Arad and O Levy-Ontman ldquoRed microalgal cell-wallpolysaccharides biotechnological aspectsrdquo Current Opinion inBiotechnology vol 21 no 3 pp 358ndash364 2010
[95] M Kim J H Yim S-Y Kim et al ldquoIn vitro inhibitionof influenza A virus infection by marine microalga-derivedsulfated polysaccharide p-KG03rdquoAntiviral Research vol 93 no2 pp 253ndash259 2012
[96] Z A Mohamed ldquoPolysaccharides as a protective responseagainst microcystin-induced oxidative stress in Chlorella vul-garis and Scenedesmus quadricauda and their possible signifi-cance in the aquatic ecosystemrdquo Ecotoxicology vol 17 no 6 pp504ndash516 2008
[97] T Tannin-Spitz M Bergman D Van-Moppes S Grossmanand S Arad ldquoAntioxidant activity of the polysaccharide of thered microalga Porphyridium sprdquo Journal of Applied Phycologyvol 17 no 3 pp 215ndash222 2005
[98] J W Prakash M Johnson and S Jeeva ldquoAntimicrobial activityof certain fresh water microalgae from Thamirabarani RiverTamil Nadu South Indiardquo Asian Pacific Journal of TropicalBiomedicine vol 1 supplement no 2 pp S170ndashS173 2011
[99] H M Amaro A C Guedes and F X Malcata ldquoAntimicrobialactivities of microalgae an invited reviewrdquo in Science againstMicrobial Pathogens Communicating Current Research andTechnological Advances A Mendez-Vilas Ed pp 1272ndash12802011
[100] V J Smith A PDesbois and E ADyrynda ldquoConventional andunconventional antimicrobials from fish marine invertebratesand micro-algaerdquo Marine Drugs vol 8 no 4 pp 1213ndash12622010
14 BioMed Research International
[101] M F D J Raposo A M M B de Morais and R M SC de Morais ldquoInfluence of sulphate on the composition andantibacterial and antiviral properties of the exopolysaccharidefrom Porphyridium cruentumrdquo Life Sciences vol 101 no 1-2 pp56ndash63 2014
[102] M F De Jesus Raposo R M S C De Morais and A M M BDe Morais ldquoHealth applications of bioactive compounds frommarine microalgaerdquo Life Sciences vol 93 no 15 pp 479ndash4862013
[103] A Smelcerovic Z Knezevic-Jugovic and Z PetronijevicldquoMicrobial polysaccharides and their derivatives as current andprospective pharmaceuticalsrdquo Current Pharmaceutical Designvol 14 no 29 pp 3168ndash3195 2008
[104] M T Madigan J M Martinko P V Dunlap and D P ClarkMicrobiologia de Brock Artmed Editora 12th edition 2010
[105] M G de Morais J A V Costa P H L Pranke et alldquoDevelopment of a newnanofiber scaffold for usewith stemcellsin a third degree burn animal modelrdquo Burns Oxford vol 40 no8 pp 1650ndash1660 2014
[106] M G de Morais C Stillings R Dersch et al ldquoPreparation ofnanofibers containing the microalga Spirulina (Arthrospira)rdquoBioresource Technology vol 101 no 8 pp 2872ndash2876 2010
[107] D Steffens M Lersch A Rosa et al ldquoA new biomaterialof nanofibers with the microalga Spirulina as scaffolds tocultivate with stem cells for use in tissue engineeringrdquo Journalof Biomedical Nanotechnology vol 9 no 4 pp 710ndash718 2013
[108] C Barrow and F ShahidiMarine Nutraceuticals and FunctionalFoods CRC Press Taylor amp Francis Boca Raton Fla USA2008
[109] M N A Khan J-Y ChoM-C Lee et al ldquoIsolation of two anti-inflammatory and one pro-inflammatory polyunsaturated fattyacids from the brown seaweed Undaria pinnatifidardquo Journal ofAgricultural and Food Chemistry vol 55 no 17 pp 6984ndash69882007
[110] M S Matsui N Muizzuddin S Arad and K MarenusldquoSulfated polysaccharides from redmicroalgae have antiinflam-matory properties in vitro and in vivordquo Applied Biochemistryand Biotechnology vol 104 no 1 pp 13ndash22 2003
[111] V B Bhat and K M Madyastha ldquoScavenging of peroxynitriteby phycocyanin and phycocyanobilin from Spirulina platensisprotection against oxidative damage to DNArdquo Biochemical andBiophysical Research Communications vol 285 no 2 pp 262ndash266 2001
[112] I A Schepetkin and M T Quinn ldquoBotanical polysaccharidesmacrophage immunomodulation and therapeutic potentialrdquoInternational Immunopharmacology vol 6 no 3 pp 317ndash3332006
[113] J K Park Z-H Kim C G Lee et al ldquoCharacterization andimmunostimulating activity of a water-soluble polysaccharideisolated from Haematococcus lacustrisrdquo Biotechnology and Bio-process Engineering vol 16 no 6 pp 1090ndash1098 2011
[114] S Guzman A Gato M Lamela M Freire-Garabal and J MCalleja ldquoAnti-inflammatory and immunomodulatory activitiesof polysaccharide from Chlorella stigmatophora and Phaeo-dactylum tricornutumrdquo Phytotherapy Research vol 17 no 6 pp665ndash670 2003
[115] E Ryckebosch C Bruneel R Termote-Verhalle K Goiris KMuylaert and I Foubert ldquoNutritional evaluation of microalgaeoils rich in omega-3 long chain polyunsaturated fatty acids as analternative for fish oilrdquo Food Chemistry vol 160 pp 393ndash4002014
[116] P Zhao Z Zang X Xie A Huang and G Wang ldquoTheinfluence of different flocculants on the physiological activityand fucoxanthin production of Phaeodactylum tricornutumrdquoProcess Biochemistry vol 49 no 4 pp 681ndash687 2014
[117] D Moreau C Tomasoni C Jacquot et al ldquoCultivated microal-gae and the carotenoid fucoxanthin from Odontella auritaas potent anti-proliferative agents in bronchopulmonary andepithelial cell linesrdquo Environmental Toxicology and Pharmacol-ogy vol 22 no 1 pp 97ndash103 2006
[118] H Maeda M Hosokawa T Sashima K Funayama and KMiyashita ldquoFucoxanthin from edible seaweed Undaria pinnati-fida shows antiobesity effect through UCP1 expression in whiteadipose tissuesrdquo Biochemical and Biophysical Research Commu-nications vol 332 no 2 pp 392ndash397 2005
[119] J E Piero Estrada P Bermejo Bescos and A M Villar delFresno ldquoAntioxidant activity of different fractions of Spirulinaplatensis protean extractrdquo IL Farmaco vol 56 no 5ndash7 pp 497ndash500 2001
[120] S-M Kang S-J Heo K-N Kim S-H Lee and Y-JJeon ldquoIsolation and identification of new compound 2710158401015840-phloroglucinol-661015840-bieckol from brown algae Ecklonia cavaand its antioxidant effectrdquo Journal of Functional Foods vol 4no 1 pp 158ndash166 2012
[121] HHAbdEl-Baky F K El Baz andG S El-Baroty ldquoProductionof phenolic compounds from Spirulinamaximamicroalgae andits protective effectsrdquoAfrican Journal of Biotechnology vol 8 no24 pp 7059ndash7067 2009
[122] A C Guedes H M Amaro and F X Malcata ldquoMicroalgae assources of carotenoidsrdquoMarineDrugs vol 9 no 4 pp 625ndash6442011
[123] G L Renju G M Kurup and K C H Saritha ldquoEffect oflycopene from Chlorella marina on high cholesterol-inducedoxidative damage and inflammation in ratsrdquo Inflammopharma-cology vol 22 no 1 pp 45ndash54 2014
[124] G L Renju G M Kurup and C H S Kumari ldquoAnti-inflammatory activity of lycopene isolated from Chlorellamarina onType II Collagen induced arthritis in SpragueDawleyratsrdquo Immunopharmacology and Immunotoxicology vol 35 no2 pp 282ndash291 2013
[125] C Vılchez E Forjan M Cuaresma F Bedmar I Garbayo andJ M Vega ldquoMarine carotenoids biological functions andcommercial applicationsrdquo Marine Drugs vol 9 no 3 pp 319ndash333 2011
[126] G Richardson ldquoBeyond eye healthrdquo Life Extension Magazine2011 httpwwwleforgMagazine20117Beyond-Eye-HealthPage-01
[127] M Abidov Z Ramazanov R Seifulla and S Grachev ldquoTheeffects of Xanthigen in the weight management of obesepremenopausal women with non-alcoholic fatty liver diseaseand normal liver fatrdquo Diabetes Obesity and Metabolism vol 12no 1 pp 72ndash81 2010
[128] H M Ragap R H Khalil and H HMutawie ldquoImmunostimu-lant effects of dietary Spirulina platensis on tilapia Oreochromisniloticusrdquo Journal of Applied Pharmaceutical Science vol 2 no2 pp 26ndash31 2012
[129] W Xu Z Gao Z Qi M Qiu J-Q Peng and R Shao ldquoEffect ofdietary chlorella on the growth performance and physiologicalparameters of gibel carp Carassius auratus gibeliordquo TurkishJournal of Fisheries and Aquatic Sciences vol 14 no 1 pp 53ndash572014
[130] P Amaninejad H Emadi M Ematiazjoo et al ldquoEffects ofDunaliella microalgae (Dunaliella salina) on different level of
BioMed Research International 15
IgM Immunoglobulin in rainbow trout (Oncrohynchusmykiss)rdquoGlobal Journal of Biodiversity Science and Management vol 3no 2 pp 237ndash242 2013
[131] V Mimouni L Ulmann V Pasquet et al ldquoThe potential ofmicroalgae for the production of bioactive molecules of phar-maceutical interestrdquoCurrent Pharmaceutical Biotechnology vol13 no 15 pp 2733ndash2750 2012
[132] S M Tosh and S Yada ldquoDietary fibres in pulse seeds and frac-tions characterization functional attributes and applicationsrdquoFood Research International vol 43 no 2 pp 450ndash460 2010
[133] H M Amaro R Barros A C Guedes I Sousa-Pinto and FXMalcata ldquoMicroalgal compoundsmodulate carcinogenesis inthe gastrointestinal tractrdquo Trends in Biotechnology vol 31 no 2pp 92ndash98 2013
[134] S S M Mostafa ldquoMicroalgal biotechnology prospects andapplicationsrdquo in Plant Science chapter 12 pp 275ndash314 InTech2012
[135] L Custodio T Justo L Silvestre et al ldquoMicroalgae of dif-ferent phyla display antioxidant metal chelating and acetyl-cholinesterase inhibitory activitiesrdquoFoodChemistry vol 131 no1 pp 134ndash140 2012
[136] C-CHu J-T Lin F-J Lu F-P Chou andD-J Yang ldquoDetermi-nation of carotenoids in Dunaliella salina cultivated in Taiwanand antioxidant capacity of the algal carotenoid extractrdquo FoodChemistry vol 109 no 2 pp 439ndash446 2008
[34] M Temina H Rezankova T Rezanka and V M DembitskyldquoDiversity of the fatty acids of the Nostoc species and theirstatistical analysisrdquoMicrobiological Research vol 162 no 4 pp308ndash321 2007
[35] Z Deng Q Hu F Lu G Liu and Z Hu ldquoColony developmentand physiological characterization of the edible blue-greenalga Nostoc sphaeroides (Nostocaceae Cyanophyta)rdquo Progressin Natural Science vol 18 no 12 pp 1475ndash1484 2008
[36] M R Boyd K R Gustafson J B McMahon et al ldquoDiscoveryof cyanovirin-N a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycopro-tein gp120 potential applications to microbicide developmentrdquoAntimicrobial Agents and Chemotherapy vol 41 no 7 pp 1521ndash1530 1997
[37] M Wang Y-N Xu G-Z Jiang L-B Li and T-Y KuangldquoMembrane lipids and their fatty acid composition in Nostocflagelliforme cellsrdquoActa Botanica Sinica vol 42 no 12 pp 1263ndash1266 2000
[38] J Masojıdek and O Prasil ldquoThe development of microalgalbiotechnology in the Czech Republicrdquo Journal of IndustrialMicrobiology amp Biotechnology vol 37 no 12 pp 1307ndash1317 2010
[39] M Plaza M Herrero A Alejandro Cifuentes and E IbanezldquoInnovative natural functional ingredients from microalgaerdquoJournal of Agricultural and Food Chemistry vol 57 no 16 pp7159ndash7170 2009
[40] J A V Costa E M Radmann V S Cerqueira G C Santosand M N Calheiros ldquoPerfil de acidos graxos das microalgasChlorella vulgaris e Chlorella minutissima cultivadas em difer-entes condicoesrdquo Alimentos e Nutricao Araraquara vol 17 no4 pp 429ndash436 2006
[41] K H Cha S W Kang C Y Kim B H Um Y R Naand C-H Pan ldquoEffect of pressurized liquids on extraction ofantioxidants from chlorella vulgarisrdquo Journal of Agricultural andFood Chemistry vol 58 no 8 pp 4756ndash4761 2010
[42] F Kokou P Makridis M Kentouri and P Divanach ldquoAntibac-terial activity inmicroalgae culturesrdquoAquaculture Research vol43 no 10 pp 1520ndash1527 2012
[43] L Li W Li Y-H Kim and YW Lee ldquoChlorella vulgaris extractameliorates carbon tetrachloride-induced acute hepatic injuryin micerdquo Experimental and Toxicologic Pathology vol 65 no 1-2 pp 73ndash80 2013
[44] N B Medina-Jaritz L F Carmona-Ugalde J C Lopez-CedilloandF S L Ruiloba-DeLeon ldquoAntibacterial activity ofmethano-lic extracts from Dunaliella salina and Chlorella vulgarisrdquo TheFASEB Journal vol 27 abstract 11675 2013
[45] L Zhao and B V Sweet ldquoLutein and zeaxanthin for maculardegenerationrdquo The American Journal of Health-System Phar-macy vol 65 no 13 pp 1232ndash1238 2008
[46] P Spolaore C Joannis-Cassan E Duran and A IsambertldquoCommercial applications of microalgaerdquo Journal of Bioscienceand Bioengineering vol 101 no 2 pp 87ndash96 2006
[47] C Rosch and C Posten ldquoChallenges and perspectives ofmicroalgae productionrdquo TechnikfolgenabschatzungmdashTheorieund Praxis vol 21 no 1 2012
[48] K Preetha L John C S Subin and K K Vijayan ldquoPhenotypicand genetic characterization of Dunaliella (Chlorophyta) fromIndian salinas and their diversityrdquoAquatic Biosystems vol 8 no1 article 27 2012
[49] A Hosseini Tafreshi and M Shariati ldquoDunaliella biotechnol-ogy methods and applicationsrdquo Journal of Applied Microbiol-ogy vol 107 no 1 pp 14ndash35 2009
[50] M Francavilla P Trotta and R Luque ldquoPhytosterols fromDunaliella tertiolecta and Dunaliella salina a potentially novelindustrial applicationrdquo Bioresource Technology vol 101 no 11pp 4144ndash4150 2010
[51] F F Madkour and M M Abdel-Daim ldquoHepatoprotective andantioxidant activity of dunaliella salina in paracetamol-inducedacute toxicity in ratsrdquo Indian Journal of Pharmaceutical Sciencesvol 75 no 6 pp 642ndash648 2013
[52] T Chang S Ohta N Ikegami H Miyata T Kashimoto andM Kondo ldquoAntibiotic substances produced by a marine greenalgaDunaliella primolectardquo Bioresource Technology vol 44 no2 pp 149ndash153 1993
[53] M Herrero L Jaime P J Martın-Alvarez A Cifuentes and EIbanez ldquoOptimization of the extraction of antioxidants fromDunaliella salina microalga by pressurized liquidsrdquo Journal ofAgricultural and Food Chemistry vol 54 no 15 pp 5597ndash56032006
[54] R Leon M Martın J Vigara C Vilchez and J MVega ldquoMicroalgae mediated photoproduction of 120573-carotene inaqueous-organic two phase systemsrdquo Biomolecular Engineeringvol 20 no 4ndash6 pp 177ndash182 2003
[55] M Garcıa-Gonzalez J Moreno J C Manzano F J Florencioand M G Guerrero ldquoProduction of Dunaliella salina biomassrich in 9-119888119894119904-120573-carotene and lutein in a closed tubular photo-bioreactorrdquo Journal of Biotechnology vol 115 no 1 pp 81ndash902005
[56] D M M Kleinegris M Janssen W A Brandenburg andR H Wijffels ldquoContinuous production of carotenoids fromDunaliella salinardquo Enzyme and Microbial Technology vol 48no 3 pp 253ndash259 2011
[57] P Stolz and B Obermayer ldquoManufacturing microalgae for skincarerdquo Cosmetics amp Toiletries Science Applied vol 120 pp 99ndash106 2005
[58] M N Noaman ldquoEffect of potassium and nitrogen fertilizers onthe growth and biomass of some halophytes grown under highlevels of salinityrdquo Journal of Agronomy vol 3 no 1 pp 25ndash302004
[59] S O Lourenco Cultivo de Microalgas Marinhas Princıpios eAplicacoes RiMa Sao Paulo Brazil 2006
[60] G E Fogg ldquoThe ecological significance of extracellular prod-ucts of phytoplankton photosynthesisrdquo Botanica Marina vol26 no 1 pp 3ndash14 1983
[61] D L Nelson and M M Cox Princıpios de Bioquımica SarvierSao Paulo Brazil 4th edition 2004
[62] T Chrismadha andM A Borowitzka ldquoEffect of cell density andirradiance on growth proximate composition and eicosapen-taenoic acid production of Phaeodactylum tricornutum grownin a tubular photobioreactorrdquo Journal of Applied Phycology vol6 no 1 pp 67ndash74 1994
[63] A C Guedes L A Meireles H M Amaro and F X MalcataldquoChanges in lipid class and fatty acid composition of culturesof Pavlova lutheri in response to light intensityrdquo Journal of theAmerican Oil Chemistsrsquo Society vol 87 no 7 pp 791ndash801 2010
[64] H K Madhyastha S Sivashankari and T M Vatsala ldquoC-phycocyanin from Spirulina fussiformis exposed to blue lightdemonstrates higher efficacy of in vitro antioxidant activityrdquoBiochemical Engineering Journal vol 43 no 2 pp 221ndash2242009
[65] A Vonshak Spirulina platensis (Athrospira) Physiology Cell-Biology and Biotechnoloby Taylor amp Francis London UK 1997
[66] R D Fox Spirulina Production amp Potential Edisud ParisFrance 1996
BioMed Research International 13
[67] C U Ugwu H Aoyagi and H Uchiyama ldquoPhotobioreactorsfor mass cultivation of algaerdquo Bioresource Technology vol 99no 10 pp 4021ndash4028 2008
[68] S V Mohan M V Rohit P Chiranjeevi R Chandra and BNavaneeth ldquoHeterotrophic microalgae cultivation to synergizebiodiesel production with waste remediation progress andperspectivesrdquo Bioresource Technology 2014
[69] M G Morais and J A C Costa ldquoAn open pond system formicroalgal cultivationinrdquo in Biofuels from Algae A Pandey D-J Lee Y Chisti and C R Soccol Eds p 1 Elsevier 2014
[70] R E Lee Phycology Cambridge University Press New YorkNY USA 1980
[71] A RichmondHandbook ofMicroalgalMass Culture CRCPressBoston Mass USA 1990
[72] M Coca V M Barrocal S Lucas G Gonzalez-Benito andM T Garcıa-Cubero ldquoProtein production in Spirulina platensisbiomass using beet vinasse-supplemented culture mediardquo Foodand Bioproducts Processing 2014
[73] P-F Ip and F Chen ldquoPeroxynitrite and nitryl chloride enhanceastaxanthin production by the green microalga Chlorella zofin-giensis in heterotrophic culturerdquo Process Biochemistry vol 40no 11 pp 3595ndash3599 2005
[74] D L Alonso E-H Belarbi J M Fernandez-Sevilla JRodrıguez-Ruiz and E M Grima ldquoAcyl lipid compositionvariation related to culture age and nitrogen concentration incontinuous culture of the microalga Phaeodactylum tricornu-tumrdquo Phytochemistry vol 54 no 5 pp 461ndash471 2000
[75] W Schmidell A U Lima E Aquarone and W BorzaniBiotecnologia Industrial Volume 2 Edgard Blucher Sao PauloBrazil 2001
[76] R R L Guillard ldquoCulture of phytoplankton for feeding marineinvertebratesrdquo in Culture of Marine Invertebrate Animals W LSmith and M H Chanley Eds pp 29ndash60 Plenum New YorkNY USA 1975
[77] R Pangestuti and S-K Kim ldquoBiological activities and healthbenefit effects of natural pigments derived from marine algaerdquoJournal of Functional Foods vol 3 no 4 pp 255ndash266 2011
[78] K Skjanes C Rebours and P Lindblad ldquoPotential for greenmicroalgae to produce hydrogen pharmaceuticals and otherhigh value products in a combined processrdquo Critical Reviews inBiotechnology vol 33 no 2 pp 172ndash215 2013
[79] I Rodrıguez-Meizoso L Jaime S Santoyo F J Senorans ACifuentes and E Ibanez ldquoSubcritical water extraction andcharacterization of bioactive compounds from Haematococcuspluvialis microalgardquo Journal of Pharmaceutical and BiomedicalAnalysis vol 51 no 2 pp 456ndash463 2010
[80] M Herrero M Castro-Puyana J A Mendiola and E IbanezldquoCompressed fluids for the extraction of bioactive compoundsrdquoTrends in Analytical Chemistry vol 43 pp 67ndash83 2013
[81] N K Singh and D W Dhar ldquoMicroalgae as second generationbiofuel A reviewrdquo Agronomy for Sustainable Development vol31 no 4 pp 605ndash629 2011
[82] L Brennan and P Owende ldquoBiofuels frommicroalgae towardsmeeting advanced fuel standardsrdquo in Advanced Biofuels andBioproducts JW Lee Ed pp 553ndash599 Springer NewYork NYUSA 2013
[83] A Singh P S Nigam and J D Murphy ldquoRenewable fuels fromalgae an answer to debatable land based fuelsrdquo BioresourceTechnology vol 102 no 1 pp 10ndash16 2011
[84] P Perez-Lopez S Gonzalez-Garcıa R G Ulloa J SineiroG Feijoo and M T Moreira ldquoLife cycle assessment of the
production of bioactive compounds from Tetraselmis suecica atpilot scalerdquo Journal of Cleaner Production vol 64 pp 323ndash3312014
[85] B Subhadra ldquoAlgal biorefinery-based industry an approachto address fuel and food insecurity for a carbon-smart worldrdquoJournal of the Science of Food and Agriculture vol 91 no 1 pp2ndash13 2011
[86] D J Newman and G M Cragg ldquoNatural products as sourcesof new drugs over the 30 years from 1981 to 2010rdquo Journal ofNatural Products vol 75 no 3 pp 311ndash335 2012
[87] H-B Li K-W Cheng C-C Wong K-W Fan F Chen andY Jiang ldquoEvaluation of antioxidant capacity and total phenoliccontent of different fractions of selected microalgaerdquo FoodChemistry vol 102 no 3 pp 771ndash776 2007
[88] T M Mata A A Martins and N S Caetano ldquoMicroalgaefor biodiesel production and other applications a reviewrdquoRenewable and Sustainable EnergyReviews vol 14 no 1 pp 217ndash232 2010
[89] A Gupta and J K Sainis ldquoIsolation of C-phycocyanin fromSynechococcus sp (Anacystis nidulans BD1)rdquo Journal of AppliedPhycology vol 22 no 3 pp 231ndash233 2010
[90] P J Viskari and C L Colyer ldquoRapid extraction of phyco-biliproteins from cultured cyanobacteria samplesrdquo AnalyticalBiochemistry vol 319 no 2 pp 263ndash271 2003
[91] R Bermejo Roman J M Alvarez-Pez F G Acien Fernandezand E Molina Grima ldquoRecovery of pure B-phycoerythrin fromthe microalga Porphyridium cruentumrdquo Journal of Biotechnol-ogy vol 93 no 1 pp 73ndash85 2002
[92] C I Cazzonelli ldquoCarotenoids in nature insights from plantsand beyondrdquo Functional Plant Biology vol 38 no 11 pp 833ndash847 2011
[93] M A Hejazi and R HWijffels ldquoMilking of microalgaerdquo Trendsin Biotechnology vol 22 no 4 pp 189ndash194 2004
[94] S Arad and O Levy-Ontman ldquoRed microalgal cell-wallpolysaccharides biotechnological aspectsrdquo Current Opinion inBiotechnology vol 21 no 3 pp 358ndash364 2010
[95] M Kim J H Yim S-Y Kim et al ldquoIn vitro inhibitionof influenza A virus infection by marine microalga-derivedsulfated polysaccharide p-KG03rdquoAntiviral Research vol 93 no2 pp 253ndash259 2012
[96] Z A Mohamed ldquoPolysaccharides as a protective responseagainst microcystin-induced oxidative stress in Chlorella vul-garis and Scenedesmus quadricauda and their possible signifi-cance in the aquatic ecosystemrdquo Ecotoxicology vol 17 no 6 pp504ndash516 2008
[97] T Tannin-Spitz M Bergman D Van-Moppes S Grossmanand S Arad ldquoAntioxidant activity of the polysaccharide of thered microalga Porphyridium sprdquo Journal of Applied Phycologyvol 17 no 3 pp 215ndash222 2005
[98] J W Prakash M Johnson and S Jeeva ldquoAntimicrobial activityof certain fresh water microalgae from Thamirabarani RiverTamil Nadu South Indiardquo Asian Pacific Journal of TropicalBiomedicine vol 1 supplement no 2 pp S170ndashS173 2011
[99] H M Amaro A C Guedes and F X Malcata ldquoAntimicrobialactivities of microalgae an invited reviewrdquo in Science againstMicrobial Pathogens Communicating Current Research andTechnological Advances A Mendez-Vilas Ed pp 1272ndash12802011
[100] V J Smith A PDesbois and E ADyrynda ldquoConventional andunconventional antimicrobials from fish marine invertebratesand micro-algaerdquo Marine Drugs vol 8 no 4 pp 1213ndash12622010
14 BioMed Research International
[101] M F D J Raposo A M M B de Morais and R M SC de Morais ldquoInfluence of sulphate on the composition andantibacterial and antiviral properties of the exopolysaccharidefrom Porphyridium cruentumrdquo Life Sciences vol 101 no 1-2 pp56ndash63 2014
[102] M F De Jesus Raposo R M S C De Morais and A M M BDe Morais ldquoHealth applications of bioactive compounds frommarine microalgaerdquo Life Sciences vol 93 no 15 pp 479ndash4862013
[103] A Smelcerovic Z Knezevic-Jugovic and Z PetronijevicldquoMicrobial polysaccharides and their derivatives as current andprospective pharmaceuticalsrdquo Current Pharmaceutical Designvol 14 no 29 pp 3168ndash3195 2008
[104] M T Madigan J M Martinko P V Dunlap and D P ClarkMicrobiologia de Brock Artmed Editora 12th edition 2010
[105] M G de Morais J A V Costa P H L Pranke et alldquoDevelopment of a newnanofiber scaffold for usewith stemcellsin a third degree burn animal modelrdquo Burns Oxford vol 40 no8 pp 1650ndash1660 2014
[106] M G de Morais C Stillings R Dersch et al ldquoPreparation ofnanofibers containing the microalga Spirulina (Arthrospira)rdquoBioresource Technology vol 101 no 8 pp 2872ndash2876 2010
[107] D Steffens M Lersch A Rosa et al ldquoA new biomaterialof nanofibers with the microalga Spirulina as scaffolds tocultivate with stem cells for use in tissue engineeringrdquo Journalof Biomedical Nanotechnology vol 9 no 4 pp 710ndash718 2013
[108] C Barrow and F ShahidiMarine Nutraceuticals and FunctionalFoods CRC Press Taylor amp Francis Boca Raton Fla USA2008
[109] M N A Khan J-Y ChoM-C Lee et al ldquoIsolation of two anti-inflammatory and one pro-inflammatory polyunsaturated fattyacids from the brown seaweed Undaria pinnatifidardquo Journal ofAgricultural and Food Chemistry vol 55 no 17 pp 6984ndash69882007
[110] M S Matsui N Muizzuddin S Arad and K MarenusldquoSulfated polysaccharides from redmicroalgae have antiinflam-matory properties in vitro and in vivordquo Applied Biochemistryand Biotechnology vol 104 no 1 pp 13ndash22 2003
[111] V B Bhat and K M Madyastha ldquoScavenging of peroxynitriteby phycocyanin and phycocyanobilin from Spirulina platensisprotection against oxidative damage to DNArdquo Biochemical andBiophysical Research Communications vol 285 no 2 pp 262ndash266 2001
[112] I A Schepetkin and M T Quinn ldquoBotanical polysaccharidesmacrophage immunomodulation and therapeutic potentialrdquoInternational Immunopharmacology vol 6 no 3 pp 317ndash3332006
[113] J K Park Z-H Kim C G Lee et al ldquoCharacterization andimmunostimulating activity of a water-soluble polysaccharideisolated from Haematococcus lacustrisrdquo Biotechnology and Bio-process Engineering vol 16 no 6 pp 1090ndash1098 2011
[114] S Guzman A Gato M Lamela M Freire-Garabal and J MCalleja ldquoAnti-inflammatory and immunomodulatory activitiesof polysaccharide from Chlorella stigmatophora and Phaeo-dactylum tricornutumrdquo Phytotherapy Research vol 17 no 6 pp665ndash670 2003
[115] E Ryckebosch C Bruneel R Termote-Verhalle K Goiris KMuylaert and I Foubert ldquoNutritional evaluation of microalgaeoils rich in omega-3 long chain polyunsaturated fatty acids as analternative for fish oilrdquo Food Chemistry vol 160 pp 393ndash4002014
[116] P Zhao Z Zang X Xie A Huang and G Wang ldquoTheinfluence of different flocculants on the physiological activityand fucoxanthin production of Phaeodactylum tricornutumrdquoProcess Biochemistry vol 49 no 4 pp 681ndash687 2014
[117] D Moreau C Tomasoni C Jacquot et al ldquoCultivated microal-gae and the carotenoid fucoxanthin from Odontella auritaas potent anti-proliferative agents in bronchopulmonary andepithelial cell linesrdquo Environmental Toxicology and Pharmacol-ogy vol 22 no 1 pp 97ndash103 2006
[118] H Maeda M Hosokawa T Sashima K Funayama and KMiyashita ldquoFucoxanthin from edible seaweed Undaria pinnati-fida shows antiobesity effect through UCP1 expression in whiteadipose tissuesrdquo Biochemical and Biophysical Research Commu-nications vol 332 no 2 pp 392ndash397 2005
[119] J E Piero Estrada P Bermejo Bescos and A M Villar delFresno ldquoAntioxidant activity of different fractions of Spirulinaplatensis protean extractrdquo IL Farmaco vol 56 no 5ndash7 pp 497ndash500 2001
[120] S-M Kang S-J Heo K-N Kim S-H Lee and Y-JJeon ldquoIsolation and identification of new compound 2710158401015840-phloroglucinol-661015840-bieckol from brown algae Ecklonia cavaand its antioxidant effectrdquo Journal of Functional Foods vol 4no 1 pp 158ndash166 2012
[121] HHAbdEl-Baky F K El Baz andG S El-Baroty ldquoProductionof phenolic compounds from Spirulinamaximamicroalgae andits protective effectsrdquoAfrican Journal of Biotechnology vol 8 no24 pp 7059ndash7067 2009
[122] A C Guedes H M Amaro and F X Malcata ldquoMicroalgae assources of carotenoidsrdquoMarineDrugs vol 9 no 4 pp 625ndash6442011
[123] G L Renju G M Kurup and K C H Saritha ldquoEffect oflycopene from Chlorella marina on high cholesterol-inducedoxidative damage and inflammation in ratsrdquo Inflammopharma-cology vol 22 no 1 pp 45ndash54 2014
[124] G L Renju G M Kurup and C H S Kumari ldquoAnti-inflammatory activity of lycopene isolated from Chlorellamarina onType II Collagen induced arthritis in SpragueDawleyratsrdquo Immunopharmacology and Immunotoxicology vol 35 no2 pp 282ndash291 2013
[125] C Vılchez E Forjan M Cuaresma F Bedmar I Garbayo andJ M Vega ldquoMarine carotenoids biological functions andcommercial applicationsrdquo Marine Drugs vol 9 no 3 pp 319ndash333 2011
[126] G Richardson ldquoBeyond eye healthrdquo Life Extension Magazine2011 httpwwwleforgMagazine20117Beyond-Eye-HealthPage-01
[127] M Abidov Z Ramazanov R Seifulla and S Grachev ldquoTheeffects of Xanthigen in the weight management of obesepremenopausal women with non-alcoholic fatty liver diseaseand normal liver fatrdquo Diabetes Obesity and Metabolism vol 12no 1 pp 72ndash81 2010
[128] H M Ragap R H Khalil and H HMutawie ldquoImmunostimu-lant effects of dietary Spirulina platensis on tilapia Oreochromisniloticusrdquo Journal of Applied Pharmaceutical Science vol 2 no2 pp 26ndash31 2012
[129] W Xu Z Gao Z Qi M Qiu J-Q Peng and R Shao ldquoEffect ofdietary chlorella on the growth performance and physiologicalparameters of gibel carp Carassius auratus gibeliordquo TurkishJournal of Fisheries and Aquatic Sciences vol 14 no 1 pp 53ndash572014
[130] P Amaninejad H Emadi M Ematiazjoo et al ldquoEffects ofDunaliella microalgae (Dunaliella salina) on different level of
BioMed Research International 15
IgM Immunoglobulin in rainbow trout (Oncrohynchusmykiss)rdquoGlobal Journal of Biodiversity Science and Management vol 3no 2 pp 237ndash242 2013
[131] V Mimouni L Ulmann V Pasquet et al ldquoThe potential ofmicroalgae for the production of bioactive molecules of phar-maceutical interestrdquoCurrent Pharmaceutical Biotechnology vol13 no 15 pp 2733ndash2750 2012
[132] S M Tosh and S Yada ldquoDietary fibres in pulse seeds and frac-tions characterization functional attributes and applicationsrdquoFood Research International vol 43 no 2 pp 450ndash460 2010
[133] H M Amaro R Barros A C Guedes I Sousa-Pinto and FXMalcata ldquoMicroalgal compoundsmodulate carcinogenesis inthe gastrointestinal tractrdquo Trends in Biotechnology vol 31 no 2pp 92ndash98 2013
[134] S S M Mostafa ldquoMicroalgal biotechnology prospects andapplicationsrdquo in Plant Science chapter 12 pp 275ndash314 InTech2012
[135] L Custodio T Justo L Silvestre et al ldquoMicroalgae of dif-ferent phyla display antioxidant metal chelating and acetyl-cholinesterase inhibitory activitiesrdquoFoodChemistry vol 131 no1 pp 134ndash140 2012
[136] C-CHu J-T Lin F-J Lu F-P Chou andD-J Yang ldquoDetermi-nation of carotenoids in Dunaliella salina cultivated in Taiwanand antioxidant capacity of the algal carotenoid extractrdquo FoodChemistry vol 109 no 2 pp 439ndash446 2008
[67] C U Ugwu H Aoyagi and H Uchiyama ldquoPhotobioreactorsfor mass cultivation of algaerdquo Bioresource Technology vol 99no 10 pp 4021ndash4028 2008
[68] S V Mohan M V Rohit P Chiranjeevi R Chandra and BNavaneeth ldquoHeterotrophic microalgae cultivation to synergizebiodiesel production with waste remediation progress andperspectivesrdquo Bioresource Technology 2014
[69] M G Morais and J A C Costa ldquoAn open pond system formicroalgal cultivationinrdquo in Biofuels from Algae A Pandey D-J Lee Y Chisti and C R Soccol Eds p 1 Elsevier 2014
[70] R E Lee Phycology Cambridge University Press New YorkNY USA 1980
[71] A RichmondHandbook ofMicroalgalMass Culture CRCPressBoston Mass USA 1990
[72] M Coca V M Barrocal S Lucas G Gonzalez-Benito andM T Garcıa-Cubero ldquoProtein production in Spirulina platensisbiomass using beet vinasse-supplemented culture mediardquo Foodand Bioproducts Processing 2014
[73] P-F Ip and F Chen ldquoPeroxynitrite and nitryl chloride enhanceastaxanthin production by the green microalga Chlorella zofin-giensis in heterotrophic culturerdquo Process Biochemistry vol 40no 11 pp 3595ndash3599 2005
[74] D L Alonso E-H Belarbi J M Fernandez-Sevilla JRodrıguez-Ruiz and E M Grima ldquoAcyl lipid compositionvariation related to culture age and nitrogen concentration incontinuous culture of the microalga Phaeodactylum tricornu-tumrdquo Phytochemistry vol 54 no 5 pp 461ndash471 2000
[75] W Schmidell A U Lima E Aquarone and W BorzaniBiotecnologia Industrial Volume 2 Edgard Blucher Sao PauloBrazil 2001
[76] R R L Guillard ldquoCulture of phytoplankton for feeding marineinvertebratesrdquo in Culture of Marine Invertebrate Animals W LSmith and M H Chanley Eds pp 29ndash60 Plenum New YorkNY USA 1975
[77] R Pangestuti and S-K Kim ldquoBiological activities and healthbenefit effects of natural pigments derived from marine algaerdquoJournal of Functional Foods vol 3 no 4 pp 255ndash266 2011
[78] K Skjanes C Rebours and P Lindblad ldquoPotential for greenmicroalgae to produce hydrogen pharmaceuticals and otherhigh value products in a combined processrdquo Critical Reviews inBiotechnology vol 33 no 2 pp 172ndash215 2013
[79] I Rodrıguez-Meizoso L Jaime S Santoyo F J Senorans ACifuentes and E Ibanez ldquoSubcritical water extraction andcharacterization of bioactive compounds from Haematococcuspluvialis microalgardquo Journal of Pharmaceutical and BiomedicalAnalysis vol 51 no 2 pp 456ndash463 2010
[80] M Herrero M Castro-Puyana J A Mendiola and E IbanezldquoCompressed fluids for the extraction of bioactive compoundsrdquoTrends in Analytical Chemistry vol 43 pp 67ndash83 2013
[81] N K Singh and D W Dhar ldquoMicroalgae as second generationbiofuel A reviewrdquo Agronomy for Sustainable Development vol31 no 4 pp 605ndash629 2011
[82] L Brennan and P Owende ldquoBiofuels frommicroalgae towardsmeeting advanced fuel standardsrdquo in Advanced Biofuels andBioproducts JW Lee Ed pp 553ndash599 Springer NewYork NYUSA 2013
[83] A Singh P S Nigam and J D Murphy ldquoRenewable fuels fromalgae an answer to debatable land based fuelsrdquo BioresourceTechnology vol 102 no 1 pp 10ndash16 2011
[84] P Perez-Lopez S Gonzalez-Garcıa R G Ulloa J SineiroG Feijoo and M T Moreira ldquoLife cycle assessment of the
production of bioactive compounds from Tetraselmis suecica atpilot scalerdquo Journal of Cleaner Production vol 64 pp 323ndash3312014
[85] B Subhadra ldquoAlgal biorefinery-based industry an approachto address fuel and food insecurity for a carbon-smart worldrdquoJournal of the Science of Food and Agriculture vol 91 no 1 pp2ndash13 2011
[86] D J Newman and G M Cragg ldquoNatural products as sourcesof new drugs over the 30 years from 1981 to 2010rdquo Journal ofNatural Products vol 75 no 3 pp 311ndash335 2012
[87] H-B Li K-W Cheng C-C Wong K-W Fan F Chen andY Jiang ldquoEvaluation of antioxidant capacity and total phenoliccontent of different fractions of selected microalgaerdquo FoodChemistry vol 102 no 3 pp 771ndash776 2007
[88] T M Mata A A Martins and N S Caetano ldquoMicroalgaefor biodiesel production and other applications a reviewrdquoRenewable and Sustainable EnergyReviews vol 14 no 1 pp 217ndash232 2010
[89] A Gupta and J K Sainis ldquoIsolation of C-phycocyanin fromSynechococcus sp (Anacystis nidulans BD1)rdquo Journal of AppliedPhycology vol 22 no 3 pp 231ndash233 2010
[90] P J Viskari and C L Colyer ldquoRapid extraction of phyco-biliproteins from cultured cyanobacteria samplesrdquo AnalyticalBiochemistry vol 319 no 2 pp 263ndash271 2003
[91] R Bermejo Roman J M Alvarez-Pez F G Acien Fernandezand E Molina Grima ldquoRecovery of pure B-phycoerythrin fromthe microalga Porphyridium cruentumrdquo Journal of Biotechnol-ogy vol 93 no 1 pp 73ndash85 2002
[92] C I Cazzonelli ldquoCarotenoids in nature insights from plantsand beyondrdquo Functional Plant Biology vol 38 no 11 pp 833ndash847 2011
[93] M A Hejazi and R HWijffels ldquoMilking of microalgaerdquo Trendsin Biotechnology vol 22 no 4 pp 189ndash194 2004
[94] S Arad and O Levy-Ontman ldquoRed microalgal cell-wallpolysaccharides biotechnological aspectsrdquo Current Opinion inBiotechnology vol 21 no 3 pp 358ndash364 2010
[95] M Kim J H Yim S-Y Kim et al ldquoIn vitro inhibitionof influenza A virus infection by marine microalga-derivedsulfated polysaccharide p-KG03rdquoAntiviral Research vol 93 no2 pp 253ndash259 2012
[96] Z A Mohamed ldquoPolysaccharides as a protective responseagainst microcystin-induced oxidative stress in Chlorella vul-garis and Scenedesmus quadricauda and their possible signifi-cance in the aquatic ecosystemrdquo Ecotoxicology vol 17 no 6 pp504ndash516 2008
[97] T Tannin-Spitz M Bergman D Van-Moppes S Grossmanand S Arad ldquoAntioxidant activity of the polysaccharide of thered microalga Porphyridium sprdquo Journal of Applied Phycologyvol 17 no 3 pp 215ndash222 2005
[98] J W Prakash M Johnson and S Jeeva ldquoAntimicrobial activityof certain fresh water microalgae from Thamirabarani RiverTamil Nadu South Indiardquo Asian Pacific Journal of TropicalBiomedicine vol 1 supplement no 2 pp S170ndashS173 2011
[99] H M Amaro A C Guedes and F X Malcata ldquoAntimicrobialactivities of microalgae an invited reviewrdquo in Science againstMicrobial Pathogens Communicating Current Research andTechnological Advances A Mendez-Vilas Ed pp 1272ndash12802011
[100] V J Smith A PDesbois and E ADyrynda ldquoConventional andunconventional antimicrobials from fish marine invertebratesand micro-algaerdquo Marine Drugs vol 8 no 4 pp 1213ndash12622010
14 BioMed Research International
[101] M F D J Raposo A M M B de Morais and R M SC de Morais ldquoInfluence of sulphate on the composition andantibacterial and antiviral properties of the exopolysaccharidefrom Porphyridium cruentumrdquo Life Sciences vol 101 no 1-2 pp56ndash63 2014
[102] M F De Jesus Raposo R M S C De Morais and A M M BDe Morais ldquoHealth applications of bioactive compounds frommarine microalgaerdquo Life Sciences vol 93 no 15 pp 479ndash4862013
[103] A Smelcerovic Z Knezevic-Jugovic and Z PetronijevicldquoMicrobial polysaccharides and their derivatives as current andprospective pharmaceuticalsrdquo Current Pharmaceutical Designvol 14 no 29 pp 3168ndash3195 2008
[104] M T Madigan J M Martinko P V Dunlap and D P ClarkMicrobiologia de Brock Artmed Editora 12th edition 2010
[105] M G de Morais J A V Costa P H L Pranke et alldquoDevelopment of a newnanofiber scaffold for usewith stemcellsin a third degree burn animal modelrdquo Burns Oxford vol 40 no8 pp 1650ndash1660 2014
[106] M G de Morais C Stillings R Dersch et al ldquoPreparation ofnanofibers containing the microalga Spirulina (Arthrospira)rdquoBioresource Technology vol 101 no 8 pp 2872ndash2876 2010
[107] D Steffens M Lersch A Rosa et al ldquoA new biomaterialof nanofibers with the microalga Spirulina as scaffolds tocultivate with stem cells for use in tissue engineeringrdquo Journalof Biomedical Nanotechnology vol 9 no 4 pp 710ndash718 2013
[108] C Barrow and F ShahidiMarine Nutraceuticals and FunctionalFoods CRC Press Taylor amp Francis Boca Raton Fla USA2008
[109] M N A Khan J-Y ChoM-C Lee et al ldquoIsolation of two anti-inflammatory and one pro-inflammatory polyunsaturated fattyacids from the brown seaweed Undaria pinnatifidardquo Journal ofAgricultural and Food Chemistry vol 55 no 17 pp 6984ndash69882007
[110] M S Matsui N Muizzuddin S Arad and K MarenusldquoSulfated polysaccharides from redmicroalgae have antiinflam-matory properties in vitro and in vivordquo Applied Biochemistryand Biotechnology vol 104 no 1 pp 13ndash22 2003
[111] V B Bhat and K M Madyastha ldquoScavenging of peroxynitriteby phycocyanin and phycocyanobilin from Spirulina platensisprotection against oxidative damage to DNArdquo Biochemical andBiophysical Research Communications vol 285 no 2 pp 262ndash266 2001
[112] I A Schepetkin and M T Quinn ldquoBotanical polysaccharidesmacrophage immunomodulation and therapeutic potentialrdquoInternational Immunopharmacology vol 6 no 3 pp 317ndash3332006
[113] J K Park Z-H Kim C G Lee et al ldquoCharacterization andimmunostimulating activity of a water-soluble polysaccharideisolated from Haematococcus lacustrisrdquo Biotechnology and Bio-process Engineering vol 16 no 6 pp 1090ndash1098 2011
[114] S Guzman A Gato M Lamela M Freire-Garabal and J MCalleja ldquoAnti-inflammatory and immunomodulatory activitiesof polysaccharide from Chlorella stigmatophora and Phaeo-dactylum tricornutumrdquo Phytotherapy Research vol 17 no 6 pp665ndash670 2003
[115] E Ryckebosch C Bruneel R Termote-Verhalle K Goiris KMuylaert and I Foubert ldquoNutritional evaluation of microalgaeoils rich in omega-3 long chain polyunsaturated fatty acids as analternative for fish oilrdquo Food Chemistry vol 160 pp 393ndash4002014
[116] P Zhao Z Zang X Xie A Huang and G Wang ldquoTheinfluence of different flocculants on the physiological activityand fucoxanthin production of Phaeodactylum tricornutumrdquoProcess Biochemistry vol 49 no 4 pp 681ndash687 2014
[117] D Moreau C Tomasoni C Jacquot et al ldquoCultivated microal-gae and the carotenoid fucoxanthin from Odontella auritaas potent anti-proliferative agents in bronchopulmonary andepithelial cell linesrdquo Environmental Toxicology and Pharmacol-ogy vol 22 no 1 pp 97ndash103 2006
[118] H Maeda M Hosokawa T Sashima K Funayama and KMiyashita ldquoFucoxanthin from edible seaweed Undaria pinnati-fida shows antiobesity effect through UCP1 expression in whiteadipose tissuesrdquo Biochemical and Biophysical Research Commu-nications vol 332 no 2 pp 392ndash397 2005
[119] J E Piero Estrada P Bermejo Bescos and A M Villar delFresno ldquoAntioxidant activity of different fractions of Spirulinaplatensis protean extractrdquo IL Farmaco vol 56 no 5ndash7 pp 497ndash500 2001
[120] S-M Kang S-J Heo K-N Kim S-H Lee and Y-JJeon ldquoIsolation and identification of new compound 2710158401015840-phloroglucinol-661015840-bieckol from brown algae Ecklonia cavaand its antioxidant effectrdquo Journal of Functional Foods vol 4no 1 pp 158ndash166 2012
[121] HHAbdEl-Baky F K El Baz andG S El-Baroty ldquoProductionof phenolic compounds from Spirulinamaximamicroalgae andits protective effectsrdquoAfrican Journal of Biotechnology vol 8 no24 pp 7059ndash7067 2009
[122] A C Guedes H M Amaro and F X Malcata ldquoMicroalgae assources of carotenoidsrdquoMarineDrugs vol 9 no 4 pp 625ndash6442011
[123] G L Renju G M Kurup and K C H Saritha ldquoEffect oflycopene from Chlorella marina on high cholesterol-inducedoxidative damage and inflammation in ratsrdquo Inflammopharma-cology vol 22 no 1 pp 45ndash54 2014
[124] G L Renju G M Kurup and C H S Kumari ldquoAnti-inflammatory activity of lycopene isolated from Chlorellamarina onType II Collagen induced arthritis in SpragueDawleyratsrdquo Immunopharmacology and Immunotoxicology vol 35 no2 pp 282ndash291 2013
[125] C Vılchez E Forjan M Cuaresma F Bedmar I Garbayo andJ M Vega ldquoMarine carotenoids biological functions andcommercial applicationsrdquo Marine Drugs vol 9 no 3 pp 319ndash333 2011
[126] G Richardson ldquoBeyond eye healthrdquo Life Extension Magazine2011 httpwwwleforgMagazine20117Beyond-Eye-HealthPage-01
[127] M Abidov Z Ramazanov R Seifulla and S Grachev ldquoTheeffects of Xanthigen in the weight management of obesepremenopausal women with non-alcoholic fatty liver diseaseand normal liver fatrdquo Diabetes Obesity and Metabolism vol 12no 1 pp 72ndash81 2010
[128] H M Ragap R H Khalil and H HMutawie ldquoImmunostimu-lant effects of dietary Spirulina platensis on tilapia Oreochromisniloticusrdquo Journal of Applied Pharmaceutical Science vol 2 no2 pp 26ndash31 2012
[129] W Xu Z Gao Z Qi M Qiu J-Q Peng and R Shao ldquoEffect ofdietary chlorella on the growth performance and physiologicalparameters of gibel carp Carassius auratus gibeliordquo TurkishJournal of Fisheries and Aquatic Sciences vol 14 no 1 pp 53ndash572014
[130] P Amaninejad H Emadi M Ematiazjoo et al ldquoEffects ofDunaliella microalgae (Dunaliella salina) on different level of
BioMed Research International 15
IgM Immunoglobulin in rainbow trout (Oncrohynchusmykiss)rdquoGlobal Journal of Biodiversity Science and Management vol 3no 2 pp 237ndash242 2013
[131] V Mimouni L Ulmann V Pasquet et al ldquoThe potential ofmicroalgae for the production of bioactive molecules of phar-maceutical interestrdquoCurrent Pharmaceutical Biotechnology vol13 no 15 pp 2733ndash2750 2012
[132] S M Tosh and S Yada ldquoDietary fibres in pulse seeds and frac-tions characterization functional attributes and applicationsrdquoFood Research International vol 43 no 2 pp 450ndash460 2010
[133] H M Amaro R Barros A C Guedes I Sousa-Pinto and FXMalcata ldquoMicroalgal compoundsmodulate carcinogenesis inthe gastrointestinal tractrdquo Trends in Biotechnology vol 31 no 2pp 92ndash98 2013
[134] S S M Mostafa ldquoMicroalgal biotechnology prospects andapplicationsrdquo in Plant Science chapter 12 pp 275ndash314 InTech2012
[135] L Custodio T Justo L Silvestre et al ldquoMicroalgae of dif-ferent phyla display antioxidant metal chelating and acetyl-cholinesterase inhibitory activitiesrdquoFoodChemistry vol 131 no1 pp 134ndash140 2012
[136] C-CHu J-T Lin F-J Lu F-P Chou andD-J Yang ldquoDetermi-nation of carotenoids in Dunaliella salina cultivated in Taiwanand antioxidant capacity of the algal carotenoid extractrdquo FoodChemistry vol 109 no 2 pp 439ndash446 2008
[101] M F D J Raposo A M M B de Morais and R M SC de Morais ldquoInfluence of sulphate on the composition andantibacterial and antiviral properties of the exopolysaccharidefrom Porphyridium cruentumrdquo Life Sciences vol 101 no 1-2 pp56ndash63 2014
[102] M F De Jesus Raposo R M S C De Morais and A M M BDe Morais ldquoHealth applications of bioactive compounds frommarine microalgaerdquo Life Sciences vol 93 no 15 pp 479ndash4862013
[103] A Smelcerovic Z Knezevic-Jugovic and Z PetronijevicldquoMicrobial polysaccharides and their derivatives as current andprospective pharmaceuticalsrdquo Current Pharmaceutical Designvol 14 no 29 pp 3168ndash3195 2008
[104] M T Madigan J M Martinko P V Dunlap and D P ClarkMicrobiologia de Brock Artmed Editora 12th edition 2010
[105] M G de Morais J A V Costa P H L Pranke et alldquoDevelopment of a newnanofiber scaffold for usewith stemcellsin a third degree burn animal modelrdquo Burns Oxford vol 40 no8 pp 1650ndash1660 2014
[106] M G de Morais C Stillings R Dersch et al ldquoPreparation ofnanofibers containing the microalga Spirulina (Arthrospira)rdquoBioresource Technology vol 101 no 8 pp 2872ndash2876 2010
[107] D Steffens M Lersch A Rosa et al ldquoA new biomaterialof nanofibers with the microalga Spirulina as scaffolds tocultivate with stem cells for use in tissue engineeringrdquo Journalof Biomedical Nanotechnology vol 9 no 4 pp 710ndash718 2013
[108] C Barrow and F ShahidiMarine Nutraceuticals and FunctionalFoods CRC Press Taylor amp Francis Boca Raton Fla USA2008
[109] M N A Khan J-Y ChoM-C Lee et al ldquoIsolation of two anti-inflammatory and one pro-inflammatory polyunsaturated fattyacids from the brown seaweed Undaria pinnatifidardquo Journal ofAgricultural and Food Chemistry vol 55 no 17 pp 6984ndash69882007
[110] M S Matsui N Muizzuddin S Arad and K MarenusldquoSulfated polysaccharides from redmicroalgae have antiinflam-matory properties in vitro and in vivordquo Applied Biochemistryand Biotechnology vol 104 no 1 pp 13ndash22 2003
[111] V B Bhat and K M Madyastha ldquoScavenging of peroxynitriteby phycocyanin and phycocyanobilin from Spirulina platensisprotection against oxidative damage to DNArdquo Biochemical andBiophysical Research Communications vol 285 no 2 pp 262ndash266 2001
[112] I A Schepetkin and M T Quinn ldquoBotanical polysaccharidesmacrophage immunomodulation and therapeutic potentialrdquoInternational Immunopharmacology vol 6 no 3 pp 317ndash3332006
[113] J K Park Z-H Kim C G Lee et al ldquoCharacterization andimmunostimulating activity of a water-soluble polysaccharideisolated from Haematococcus lacustrisrdquo Biotechnology and Bio-process Engineering vol 16 no 6 pp 1090ndash1098 2011
[114] S Guzman A Gato M Lamela M Freire-Garabal and J MCalleja ldquoAnti-inflammatory and immunomodulatory activitiesof polysaccharide from Chlorella stigmatophora and Phaeo-dactylum tricornutumrdquo Phytotherapy Research vol 17 no 6 pp665ndash670 2003
[115] E Ryckebosch C Bruneel R Termote-Verhalle K Goiris KMuylaert and I Foubert ldquoNutritional evaluation of microalgaeoils rich in omega-3 long chain polyunsaturated fatty acids as analternative for fish oilrdquo Food Chemistry vol 160 pp 393ndash4002014
[116] P Zhao Z Zang X Xie A Huang and G Wang ldquoTheinfluence of different flocculants on the physiological activityand fucoxanthin production of Phaeodactylum tricornutumrdquoProcess Biochemistry vol 49 no 4 pp 681ndash687 2014
[117] D Moreau C Tomasoni C Jacquot et al ldquoCultivated microal-gae and the carotenoid fucoxanthin from Odontella auritaas potent anti-proliferative agents in bronchopulmonary andepithelial cell linesrdquo Environmental Toxicology and Pharmacol-ogy vol 22 no 1 pp 97ndash103 2006
[118] H Maeda M Hosokawa T Sashima K Funayama and KMiyashita ldquoFucoxanthin from edible seaweed Undaria pinnati-fida shows antiobesity effect through UCP1 expression in whiteadipose tissuesrdquo Biochemical and Biophysical Research Commu-nications vol 332 no 2 pp 392ndash397 2005
[119] J E Piero Estrada P Bermejo Bescos and A M Villar delFresno ldquoAntioxidant activity of different fractions of Spirulinaplatensis protean extractrdquo IL Farmaco vol 56 no 5ndash7 pp 497ndash500 2001
[120] S-M Kang S-J Heo K-N Kim S-H Lee and Y-JJeon ldquoIsolation and identification of new compound 2710158401015840-phloroglucinol-661015840-bieckol from brown algae Ecklonia cavaand its antioxidant effectrdquo Journal of Functional Foods vol 4no 1 pp 158ndash166 2012
[121] HHAbdEl-Baky F K El Baz andG S El-Baroty ldquoProductionof phenolic compounds from Spirulinamaximamicroalgae andits protective effectsrdquoAfrican Journal of Biotechnology vol 8 no24 pp 7059ndash7067 2009
[122] A C Guedes H M Amaro and F X Malcata ldquoMicroalgae assources of carotenoidsrdquoMarineDrugs vol 9 no 4 pp 625ndash6442011
[123] G L Renju G M Kurup and K C H Saritha ldquoEffect oflycopene from Chlorella marina on high cholesterol-inducedoxidative damage and inflammation in ratsrdquo Inflammopharma-cology vol 22 no 1 pp 45ndash54 2014
[124] G L Renju G M Kurup and C H S Kumari ldquoAnti-inflammatory activity of lycopene isolated from Chlorellamarina onType II Collagen induced arthritis in SpragueDawleyratsrdquo Immunopharmacology and Immunotoxicology vol 35 no2 pp 282ndash291 2013
[125] C Vılchez E Forjan M Cuaresma F Bedmar I Garbayo andJ M Vega ldquoMarine carotenoids biological functions andcommercial applicationsrdquo Marine Drugs vol 9 no 3 pp 319ndash333 2011
[126] G Richardson ldquoBeyond eye healthrdquo Life Extension Magazine2011 httpwwwleforgMagazine20117Beyond-Eye-HealthPage-01
[127] M Abidov Z Ramazanov R Seifulla and S Grachev ldquoTheeffects of Xanthigen in the weight management of obesepremenopausal women with non-alcoholic fatty liver diseaseand normal liver fatrdquo Diabetes Obesity and Metabolism vol 12no 1 pp 72ndash81 2010
[128] H M Ragap R H Khalil and H HMutawie ldquoImmunostimu-lant effects of dietary Spirulina platensis on tilapia Oreochromisniloticusrdquo Journal of Applied Pharmaceutical Science vol 2 no2 pp 26ndash31 2012
[129] W Xu Z Gao Z Qi M Qiu J-Q Peng and R Shao ldquoEffect ofdietary chlorella on the growth performance and physiologicalparameters of gibel carp Carassius auratus gibeliordquo TurkishJournal of Fisheries and Aquatic Sciences vol 14 no 1 pp 53ndash572014
[130] P Amaninejad H Emadi M Ematiazjoo et al ldquoEffects ofDunaliella microalgae (Dunaliella salina) on different level of
BioMed Research International 15
IgM Immunoglobulin in rainbow trout (Oncrohynchusmykiss)rdquoGlobal Journal of Biodiversity Science and Management vol 3no 2 pp 237ndash242 2013
[131] V Mimouni L Ulmann V Pasquet et al ldquoThe potential ofmicroalgae for the production of bioactive molecules of phar-maceutical interestrdquoCurrent Pharmaceutical Biotechnology vol13 no 15 pp 2733ndash2750 2012
[132] S M Tosh and S Yada ldquoDietary fibres in pulse seeds and frac-tions characterization functional attributes and applicationsrdquoFood Research International vol 43 no 2 pp 450ndash460 2010
[133] H M Amaro R Barros A C Guedes I Sousa-Pinto and FXMalcata ldquoMicroalgal compoundsmodulate carcinogenesis inthe gastrointestinal tractrdquo Trends in Biotechnology vol 31 no 2pp 92ndash98 2013
[134] S S M Mostafa ldquoMicroalgal biotechnology prospects andapplicationsrdquo in Plant Science chapter 12 pp 275ndash314 InTech2012
[135] L Custodio T Justo L Silvestre et al ldquoMicroalgae of dif-ferent phyla display antioxidant metal chelating and acetyl-cholinesterase inhibitory activitiesrdquoFoodChemistry vol 131 no1 pp 134ndash140 2012
[136] C-CHu J-T Lin F-J Lu F-P Chou andD-J Yang ldquoDetermi-nation of carotenoids in Dunaliella salina cultivated in Taiwanand antioxidant capacity of the algal carotenoid extractrdquo FoodChemistry vol 109 no 2 pp 439ndash446 2008
IgM Immunoglobulin in rainbow trout (Oncrohynchusmykiss)rdquoGlobal Journal of Biodiversity Science and Management vol 3no 2 pp 237ndash242 2013
[131] V Mimouni L Ulmann V Pasquet et al ldquoThe potential ofmicroalgae for the production of bioactive molecules of phar-maceutical interestrdquoCurrent Pharmaceutical Biotechnology vol13 no 15 pp 2733ndash2750 2012
[132] S M Tosh and S Yada ldquoDietary fibres in pulse seeds and frac-tions characterization functional attributes and applicationsrdquoFood Research International vol 43 no 2 pp 450ndash460 2010
[133] H M Amaro R Barros A C Guedes I Sousa-Pinto and FXMalcata ldquoMicroalgal compoundsmodulate carcinogenesis inthe gastrointestinal tractrdquo Trends in Biotechnology vol 31 no 2pp 92ndash98 2013
[134] S S M Mostafa ldquoMicroalgal biotechnology prospects andapplicationsrdquo in Plant Science chapter 12 pp 275ndash314 InTech2012
[135] L Custodio T Justo L Silvestre et al ldquoMicroalgae of dif-ferent phyla display antioxidant metal chelating and acetyl-cholinesterase inhibitory activitiesrdquoFoodChemistry vol 131 no1 pp 134ndash140 2012
[136] C-CHu J-T Lin F-J Lu F-P Chou andD-J Yang ldquoDetermi-nation of carotenoids in Dunaliella salina cultivated in Taiwanand antioxidant capacity of the algal carotenoid extractrdquo FoodChemistry vol 109 no 2 pp 439ndash446 2008
