Review ArticleA Review of Botanical Characteristics TraditionalUsage Chemical Components Pharmacological Activitiesand Safety of Pereskia bleo (Kunth) DC
Sogand Zareisedehizadeh1 Chay-Hoon Tan2 and Hwee-Ling Koh1
1 Department of Pharmacy Faculty of Science National University of Singapore 18 Science Drive 4 Singapore 1175432Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Singapore 117597
Correspondence should be addressed to Hwee-Ling Koh phakohhlnusedusg
Received 19 February 2014 Accepted 2 May 2014 Published 3 June 2014
Academic Editor Wei Jia
Copyright copy 2014 Sogand Zareisedehizadeh 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
Pereskia bleo a leafy cactus is a medicinal plant native to West and South America and distributed in tropical and subtropicalareas It is traditionally used as a dietary vegetable barrier hedge water purifier and insect repellant and for maintaininghealth detoxification prevention of cancer andor treatment of cancer hypertension diabetes stomach ache muscle pain andinflammatory diseases such as dermatitis and rheumatismThe aim of this paper was to provide an up-to-date and comprehensivereview of the botanical characteristics traditional usage phytochemistry pharmacological activities and safety of P bleo Aliterature search using MEDLINE (via PubMed) Science direct Scopus and Google scholar and China Academic Journals Full-Text Database (CNKI) and available eBooks and books in the National University of Singapore libraries in English and Chinesewas conducted The following keywords were used Pereskia bleo Pereskia panamensis Pereskia corrugata Rhodocacus corrugatusRhodocacus bleo Cactus panamensis Cactus bleo Spinach cactus wax rose Perescia and Chinese rose This review revealed theassociation between the traditional usage of P bleo and reported pharmacological properties in the literature Further investigationon the pharmacological properties and phytoconstituents of P bleo is warranted to further exploit its potentials as a source of noveltherapeutic agents or lead compounds
1 Introduction
Pereskia bleo is a medicinal plant of the family CactaceaeCacti are well-known desert plants and widely recognized bytheir specialized growth form of the stems and leaves Thisfamily consists of 100 genera and about 2000 species [1 2]The genus Pereskia consists of 17 species with regular leafdevelopment and function They are generally representativeof the ldquoancestral cactusrdquo This genus does not look much likeother types of cacti because of having substantial leaves andthin stems [3ndash5] The plants in the genus Pereskia originatefrom the region between Brazil andMexico and South Amer-ica and Central America [6ndash8] and are cultivated in manytropical and subtropical countries including India MalaysiaSingapore and Indonesia [1] They also generally resembleother types of plants such as roses [3 8] Pereskia species are
divided into Clades A and B [9] (Table 1) The two cladesof Pereskia differ in their geographical distribution Clade Ais found around the Gulf of Mexico and the Caribbean Seawhereas Clade B is found in the south of the Amazon BasinThe stems of the species of Pereskia within Clade A begin toform bark early in the life of the plant like most non-cactiIn contrast Pereskia species within Clade B typically delayforming bark thus giving the stem the potential to becomea major organ for photosynthesis [4]
Among themPereskia aculeataMill (P aculeate)Pereskiagrandifolia Haw (P grandifolia) and Pereskia bleo (Kunth)DC (P bleo) are listed to be found in Singapore andMalaysia[7 10 11] P bleo and P grandifolia are used for medicinalpurposes in these areas [1 11] Hence more information onthese three species is presented below
Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2014 Article ID 326107 11 pageshttpdxdoiorg1011552014326107
2 Evidence-Based Complementary and Alternative Medicine
11 Pereskia aculeata Mill Its common names are Barbadosgooseberry or lemon vine [12 13] and it is native to tropicalAmerica [14] This plant is a scrambling vine growing to theheight of 10m to a tree The stems reach 2-3 cm in diameterYounger stems have hooked thorns and older stems haveclusters of woody spines The leaves are 4ndash11 cm long and15ndash4 cm wide simple and deciduous in the dry season Theflowers are white cream or pinkish with 25ndash5 cm diameterand strongly scented This plant has translucent roundedwhite to pink berries which turn to yellow or orange withthe diameter of 2 cm upon ripeningThe fruits are edible andcontaining numerous small seeds They somewhat resemblethe gooseberry in appearance and are of excellent flavor[15 16] The leaves are also edible and are a popular vegetablein parts of the Brazilian state ofMinas Gerais under the nameof ora-pro-nobis [14]
12 Pereskia grandifolia Haw It is also known as rose cac-tus or Rhodocactus grandifolia This plant is native to theNortheastern Brazil restingas and is cultivated in tropicaland subtropical areas [7] It is a shrub or small tree 2ndash5mhigh with a grayish-brown trunk up to 20 cm in diameterThe spines range from black to brown and their numberat each areole gradually increases with age The new twigsmay be spineless while the trunk may have up to 90 spinesin areoles each 2ndash65 cm long The leaves vary in sizefrom 9 to 23 cm long and the shapes range from elliptic toovate and obovate-lanceolate Usually 10ndash15 flowers of denseinflorescence develop at the ends of stems but sometimesthere are 30 or more The flowers are pink-purple and looklike rosewith 3ndash5 cmdiameter [12]The leaves ofP grandifoliaare edible [11]
13 Pereskia bleo (Kunth) DC P bleo is also known as Cactusbleo and has been commonly used for a variety of medicinaland non-medicinal purposes in different countries [1 2]However to the best of our knowledge a comprehensivereview of P bleo is not available The objective of this paper isto provide a comprehensive review of the botanical character-istics traditional usage phytoconstituents pharmacologicalactivities and safety of P bleo Such information will serve asa useful resource for the proper usage of this plant and forfuture research
2 Method
Internet sources including MEDLINE (via Pubmed) Sciencedirect Scopus and Google scholar and China Journals Full-Text Database (via CNKI) were searched for publications onthis plant The following keywords were used Pereskia bleoPereskia panamensis Pereskia corrugata Rhodocactus cor-rugatus Rhodocactus bleo Cactus panamensis Cactus bleoSpinach cactus wax rose Perescia and Chinese rose Norestriction on the language and date of publication wasimplemented In addition available books and eBooks inthe National University of Singapore (NUS) libraries weremanually searched for the relevant information
3 Results and Discussion
31 Botanical Characteristics P bleo belongs to the orderof Caryophyllales Juss ex Bercht amp J Presl superorder ofCaryophyllanae Takht and subclass of Magnoliidae Novak exTakht It is in the Cactaceae family Peresioideae subfamilyand Pereskia Mill genus [44 45] In the International PlantNomenclature Index (IPNI) [46] its ID code is 273592-2and its basionym is Cactus bleo (Kunth) Basionym name isdefined as ldquopreviously published legitimate name-bringing orepithet-bringing synonym fromwhich a new name is formedfor a taxon of different rank or position taxon of differentrank or positionrdquo [17]The scientific and common names of Pbleo are listed in Table 2 This plant is also known as ldquoPokokJarumTujuh Bilahrdquo inMalay and ldquoCak Sing Camrdquo or ldquoQi XingZhen (七星针)rdquo in Chinese [8 40] Its Chinese name literallymeans ldquoseven stars needlerdquo [7]
P bleo originates from Mesoamerica (Panama) WesternSouth America (Columbia) [1 2 6 12] and is distributedin tropical and subtropical regions [1 2] It is a deciduousshrubby tree-like plant with a height of 06ndash8m The trunkreaches 10 cm in diameter and bears very large fascicle ofspines when it is young However the trunk becomes nakedwhen turning old Young branches are red and leafy andoften bear 5ndash7 black spines up to 1 cm in length The spinesreach 2 cm on the older stems The leaves are thin oblongto oblanceolate glossy and succulent 6ndash21 cm long and 2ndash7 cm wide [2] The flowers are orange-red and grouped in 2ndash4 terminally and laterally The fruits are yellow thick walledfleshy and glossy and look like conical berries at maturityup to 5 times 5 cm in size turbinate and containing 6ndash8mm indiameter dark brown or black color seeds [1 19 31] It can bepropagated by stem cutting or seeds [12]
This species was collected by Bonpland during Hum-boldtrsquos trip through the new world and was described andpublished by Kunth in 1823 [2] In some older books andherbaria it was confused with Pereskia grandifolia (P gran-difolia) [20] because both plants are vegetatively similar [31]In addition P bleo and P grandifolia are the only exceptionsof Pereskia which grow in areas receiving considerably highannual rainfall more than 187mm per wet month OtherPereskia species grow in dry areas [3] The two speciescan be distinguished by the leaves flowers and spines Pbleo has thinner corrugated leaves and orange-red flowerswith shorter spines compared to P grandifolia In contrast
Evidence-Based Complementary and Alternative Medicine 3
Common namesButarrar (Kuna Indian) [22]Cak Sing Cam Qi xing zhen (Chinese) [1 8 23]Chupa Chupa melon Najiı Najii De Culebra Naju de esoubas and Bleo de chupa (Spanish) [2 21 24]Perescia [7]Pokok Jarum Tujuh Bilah (Malay) [2 25]Rose cactus Bleo Chinese rose Spinach cactus wax rose and orange rose cactus (English) [1 6 7 21 24 26]
Table 3 Traditional usage and methods of preparation of P bleo
Purpose Method of preparation References
Detoxification and prevention of cancer Making tea by boiling the leaves andor the fruit and then drinking itwarm or cool [27ndash30]
Dietary purposes and health maintenance Eating the raw leaf flower and fruit [19 28]Health maintenance and revitalizing thebody
Making juice from the leaves and boiling in water and drinking everymorning [30]
To alleviate muscleache Making decoction from the leaves and then using as a warm bath formuscle ache [29]
To alleviate stomachache
Preparing ldquoina kuamakaletrdquo the inflorescence is mixed with theexcrements of red ants by using a special mortar and then moistenedwith water The resulted mass is moulded to oval shape objects whichare dried in sun When using the remedy these balls are rubbed in asmall container with a small amount of water
[29]
To treat hemorrhoid hypertensiondiabetes infections headache andinflammatory conditions (rheumatismand asthma)
No information is available in the literature [28 31 32]
To neutralize the effects of the snakebites No information is available in the literature [33]
P grandifolia has thicker uncorrugated leaves pink topurplish-pink flowers and longer but fewer spines on thestems [11] Figure 1 shows the photographs of different partsof P bleo and P grandifolia Although they are differentspecies anatomical similarities in these two species supportthe evolution theory for cactus family [18]
32 Traditional Usage P bleo has been used for various pur-poses In some areas it is used as a food spice [1 7] Thisplant has been eaten raw as vegetables by some people inMalaysia and China or taken as a concoction brewed fromfresh leaves [19 36] In addition it is taken for detoxificationand revitalizing the body [27 28 40] Its fruit is consumedby some ethnic groups in Panama as a wild fruit [26] Theleaves of P bleo have been traditionally used to treat can-cer hemorrhoid hypertension diabetes [32 40] infectionsgastric pain headache ulcer and inflammatory conditions
like rheumatism and asthma [28 31] Indigenous Colombianshave used P bleo to neutralize the effects of snakebites [33]to relax spastic muscles and to alleviate muscle aches [29]Apart from dietary andmedicinal uses this plant is a suitablebarrier hedge because of its sharp spines strong stem andinsect repellant properties [21] In Central America KunaIndians used the crushed leaves to clarify drinking water[12] Different methods of preparation have been reportedfor the plant It is usually taken raw or as a decoction of itsfresh leaves Table 3 shows the traditional usage and differentpreparation methods of P bleo To the best of our knowledgeinformation on the specific preparation methods for some ofthe indicated traditional usages is not available
33 Phytochemistry The leaves are the most commonly usedpart of P bleo in traditional medicine Hence they have beenmore studied compared to the other plant parts So far 20
4 Evidence-Based Complementary and Alternative Medicine
Table 4 Reported phytoconstituents in the leaves and fruits of P bleo
Plant part Class of the constituents Constituents Reference
Fruit Carotenoids Lutein (120573e-carotene-331015840-diol) [26 37]Zeaxanthin (120573120573-carotene-331015840-diol)
Table 5 Percentage ( ww) of mineral contents in the leaves of Pbleo [38]
Mineral elements Percentage weight ()Carbon 506Oxygen 354Magnesium 04Phosphorus 04Sulfur 15Chlorine 12Potassium 102Aluminium NDlowast
Calcium 03Silicon NDFerrum (Iron) NDlowastND not detected
phytoconstituents have been reported in the leaves and twocomponents from the fruit as shown in Table 4 These com-ponents include alkaloids fatty acids glycosides lactonesphenolic sterol terpenoid and carotenoid compounds Themajor isolated component from P bleo leaves is phytol [27]In addition Doetsch et al [34] reported the isolation ofthree alkaloids namely 34-dimethoxy-120573-phenethylamine(mescaline) 3-methoxytyramine and tyramine from theleaves of this plant Vitamin E (120572-tocopherol) [36 37] which
is well known for its antioxidant properties 24-ditert-butylphenol and dihydroactinidiolide were isolated throughbioassay-guided fractionation by Malek et al [36] Murillo etal [26] analyzed the fruit of P bleo for lutein and zeaxanthincontents The total carotenoid content of the fruit was foundto be 133 120583gg making P bleo fruit a high carotenoid foodsource among the wild fruits in Panama
Themineral content of the leaves was also investigated byusing energy-dispersive X-ray microanalysis Table 5 showsthe weight percentage of the minerals reported by Abbde-wahab et al [38] As can be seen P bleo leaves are richin potassium (1016) This is more than two times of thepotassium content of tomato (45) a vegetable known tobe high in potassium [50] It has been shown that a highpotassium diet has an important role in lowering bloodpressure [51] Therefore it might be one of the possiblereasons for the traditional usage of P bleo as a treatment forhypertension [31]
34 Pharmacological Properties Pharmacological evaluationof plants is based on their traditional uses Cancer is oneof the main causes of mortality and morbidity Since Pbleo is traditionally used to prevent and treat cancer [2830 40] it has been most studied for its antiproliferativeand cancer protective properties [8 22 28 32 36 39 40]This is followed by investigations of its antimicrobial andantiparasitic effects in vitro [8 38 41ndash43 52] The snake
Evidence-Based Complementary and Alternative Medicine 5
(a) (b)
(c) (d)
(e) (f)
Figure 1 Photographs of different plant parts of P bleo and P grandifolia (a) Flower of P bleo (b) lower of P grandifolia [47] (c) stem andspines of P bleo (d) stem and spines of P grandifolia [48] (e) ripe fruits and seeds of P bleo and (f) ripe fruits and seeds of P grandifolia [49]
venom neutralizing properties [33] antinociceptive effects[35] and toxicity [22 31] of this plant have been evaluatedthrough in vivo studies
341 Antiproliferative Properties The effects of different Pbleo extracts have been reported on various cell lines in vitroThe crude methanol extract and its ethyl acetate fraction had
significant cytotoxic effects against human nasopharyngealepidermoid carcinoma cell line (KB) [36] In addition theethyl acetate fraction was more active than the methanolextract against human colon carcinoma (HCT116) and hor-mone dependent breast carcinoma cell lines (MCF7) [36]Table 6 shows the reported IC
50values (120583gmL) for the
antiproliferative effects of P bleo extracts and fractions
6 Evidence-Based Complementary and Alternative Medicine
Table6IC
50values
(120583gmL)
ofPbleo
leafextractsandfractio
nson
different
celllin
es
Cellline
Extractsandfractio
ns(IC 5
0120583gmL)
Positivec
ontro
l(IC
50120583
gmL)
Negativec
ontro
lRe
ferences
Methano
lWater
Hexane
Dichlorom
ethane
Ethylacetate
4T1
gt50
gt50
NA
NA
NA
Cisplatin
(NA)
NA
[32]
CasK
i40
5mdash
895
NA
58Doxorub
icin
(6times10minus3)
NA
[36]
CEM-ss
mdashNA
mdashmdash
mdashNA
VC[8]
HT2
9andHCT
116gt30
NA
gt30
gt30
gt30
NA
VC[8]
416
mdash675
NA
22Doxorub
icin
(36times10minus1)
NA
[36]
KB65
mdash28
NA
45
Doxorub
icin
(12times10minus2)
NA
[36]
MCF
-7gt30
NA
gt30
gt30
gt30
NA
VC[8]
39mdash
25NA
28Doxorub
icin
(75times10minus2)
NA
[36]
MRC
-5mdash
mdashmdash
NA
mdashDoxorub
icin
(55times10minus1)
NA
[36]
NIH
3T3
ge200
ge200
NA
NA
NA
Cisplatin
NA
[32]
Saos-2
mdashNA
NA
NA
NA
Cisplatin
NA
[39]
T-47D
2NA
NA
NA
NA
DNaseI
VC[40]
V79
mdashNA
NA
NA
NA
Nitracrin
eVC
[22]
IC5050
ofmaxim
umcellinhibitio
nIC
50lt20120583gmLisconsidered
activ
e100gtIC
50gt20120583gmLisrelativ
elyactiv
eandIC
50gt100isno
tactive[8]
(mdash)no
activ
ity
4T1mou
semam
marycancer
celllin
eCa
sKihu
man
cervicalcarcinom
acelllin
eCE
M-sshu
man
T-4lymph
oblasto
idcelllin
eHT2
9andHCT
116hum
ancoloncarcinom
acelllin
eKB
hum
annasoph
aryn
geal
epidermoidcarcinom
acelllin
eMCF
-7h
ormon
edependent
breastcarcinom
acelllin
eMRC
-5n
ormalhu
man
fibroblastcelllinesN
IH3T3
normalmou
sefib
roblastcelllineSaos-2hum
anosteosarcomacell
lineT-47Dhum
anbreastcarcinom
acelllineV79C
hinese
hamste
rlun
gfib
roblasts
NAnot
available
VCvehiclecontrol
Evidence-Based Complementary and Alternative Medicine 7
Table 7 Reported IC50 values (120583gmL) of selected P bleo phytoconstituents on human cell lines [28]
Compound IC50 (120583gmL) of different cell linesKB MCF7 CasKi HCT 116 A549 MRC-5
Dihydroactinidiolide 67 30 40 5 97 913120573-sitosterol gt100 72 62 gt100 78 gt10024-ditertbutylphenol 081 575 45 29 6 20120572-tocopherol 8 75 6 31 6 305Phytol 71 34 18 100 31 741Mixture of sterols gt100 gt100 gt100 gt100 gt100 gt100Doxorubicin 13 times 10minus2 76 times 10minus2 60 times 10minus3 36 times 10minus1 22 times 10minus1 55 times 10minus1
A549 human lung carcinoma cell line CasKi human cervical carcinoma cell Line HCT116 human colon carcinoma cell Line KB human nasopharyngealepidermoid carcinoma cell Line MCF-7 hormone dependent breast carcinoma cell Line MRC-5 normal human fibroblast cell Lines
Gupta et al [22] reported high tumor inhibition activityin ldquopotato disc inhibition assayrdquo using crown gall tumors(LC5077 ppm)Their result was accompanied by a significant
DNA peak reduction in the DNA intercalation test for themethanol extract of the whole plant
To date no report is available on the in vivo antiprolifer-ative activities of P bleo
(1) Cytotoxic Components Some of the cytotoxic componentsin P bleo have been reported Table 7 shows the reported IC
50
(120583gmL) values of these components in the different humancell lines The effects of these compounds and the mixture ofthe isolated sterols were not as high as doxorubicin that isa chemotherapy drug [28] In another study phytol isolatedfrom P bleo leaves was found to have a significant antitumoractivity against some mouse cancer cell lines [36]
(2) Proposed Antiproliferative Mechanism The antiprolifera-tive activity of the methanol extract of P bleo against humanbreast carcinoma cell line (T-47D) was found to be apoptoticin nature through the activation of caspase-3 and c-mycpathways [40] Caspase-3 and c-myc are frequently activateddeath proteases which catalyze the specific cleavage of manykey cellular proteins They are also essential for normaldevelopment of the tissues as well as apoptosis in the tissuesand cell types [53] Komiya et al [54] reported the inductionof apoptosis as a mechanism of action for cytotoxic activityof phytol DNA intercalation is another proposedmechanismof antiproliferative activity for P bleo [22] However in somestudies P bleo did not show appreciable cytotoxic effect [32]Differences in the sources of plants extractionmethods assaymethods and cell lines can be the possible reasons for thesediscrepancies On the other hand P bleo may contain someprodrugs which are metabolized to the active metabolitesTherefore further studies are needed to better understand itsantiproliferative activity
Apart from the cytotoxic activities against cancer celllines crudemethanol extract and its fractions (hexane waterand ethyl acetate) did not show any cytotoxicity to the normalhuman fibroblast cell lines MRC-5 [36]
342 Antioxidant Activity The adverse effects of oxida-tive stress on human health have become a serious issueOxidative stress causes production of free radicals in thebody that facilitate the development of degenerative diseasessuch as cardiovascular diseases cancers neurodegenerativedisorders [55] Alzheimerrsquos and inflammatory diseases [56]One solution to this problem is to supplement the diet withantioxidant compounds found in natural plant sources [57]Hence in the literature the antioxidant effects of P bleo wereevaluated using different assays as follows
22-Diphenyl-1-picrylhydrazyl Hydrate (DPPH) Assay Themethanol dichloromethane ethyl acetate and hexaneextracts of P bleo leaves were tested [8 25] The hexaneextract exhibited the most effective radical scavengingactivity (EC
50210 120583gmL) followed by the ethyl acetate
extract (EC50
225120583gmL) This spectrophotometric assayuses a stable radical 221015840-diphenylpicrylhydrazyl (DPPH) asa reagent [8 25]
Ferric Reducing Antioxidant Potential Assay (FRAP) Thehexane water and methanol extracts of P bleo leaves werefound to reduce Fe3+ferric cyanide complex to the ferrousform Although the reduction was statistically significant itwas not more than ascorbic acid (vitamin C) and butylatedhydroxyanisole (BHA) as positive controls [25] Hassanba-glou et al [37] compared the antioxidant activity of the ethylacetate extract with that of hexane ethanol and methanolextracts They showed that the ethyl acetate extract hadsignificantly higher antioxidant properties compared to therest of the tested extracts FRAP measures the ability of testsamples to reduce ferric ion to the ferrous form of TPTZ(246-tripyridyl-s-triazine)
120573-Carotene-Linoleic Bleaching AssayThe ethyl acetate extractof P bleo demonstrated the strongest antioxidant activityfollowed by the methanol extract reported by Sim et al [25]In this assay the linoleate free radicals formed during thereaction are neutralized by antioxidants
8 Evidence-Based Complementary and Alternative Medicine
Table8Re
ported
effectsof
Pbleo
extractson
theg
rowth
ofselected
bacteriaandfung
i
Organism
Antibacteria
land
antifun
galeffectof
thee
xtracts
Positivec
ontro
lRe
ferences
Methano
lWater
Hexane
Dichloroethane
Ethylacetate
Chloroform
Bacillussubtilisa
minusNA
minusminus
minusNA
Streptom
ycinlowast
[8]
minusminus
minusNA
minusNA
Gentamicinampicillin
[41]
NA
NA
minusminus
NA
NA
Streptom
ycin
[38]
Escherich
iacolib
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Escherich
iacolia
minusminus
minusNA
minusNA
Gentamicinampicillin
[41]
Helicobacterpylorib
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Klebsiella
pneumoniaeb
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Methicillin
resistant
Staphylococcus
aureus
aminus
NA
minus++
+minus
NA
Streptom
ycinlowast
[8]
NA
NA
minus++
NA
NA
Streptom
ycin
[38]
Mycobacteriu
msm
egmatisb
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Pseudomonas
aeruginosa
a++
NA
+++
++
NA
Streptom
ycin
[8]
+minus
minusNA
+NA
Gentamicinampicillin
[41]
NA
NA
+++
+NA
NA
Streptom
ycinlowast
[38]
Pseudomonas
aeruginosa
bminus
NA
NA
minusNA
NA
Streptom
ycin
[42]
Salm
onellacholeraesuisa
++NA
+++
minusminus
NA
Streptom
ycinlowast
[8]
NA
NA
+++
minusNA
NA
Streptom
ycin
[38]
Staphylococcus
aureus
bminus
NA
NA
minusNA
NA
Streptom
ycin
[42]
Staphylococcus
aureus
aminus
minusminus
NA
minusNA
Gentamicinampicillin
[41]
Cand
idaalbicans
cminus
minusNA
NA
NA
minusProp
icon
azolemicon
azole
[43]
Cand
idaalbicans
bminus
NA
NA
minusNA
NA
Amph
otericin
B[42]
Cladosporiu
mcucumerinum
c+
+NA
NA
NA
+Prop
icon
azolemicon
azole
[43]
a Thes
creening
fora
ntibacteria
leffectwas
carriedou
tbyd
eterminingthez
oneo
finh
ibition
usingpaperd
isc+
stand
sfor
activ
itybetween6ndash
9mm+
+sta
ndsfor
activ
itybetween9ndash
14mm+
++stands
fora
ctivity
morethan14mm
[38]
b (+)
stand
sfor
activ
ityat100120583
gmLforE
coliS
aureusK
pneum
oniaeMsmegmatis
CalbicanceP
aeruginosa
andat125120583gmLforH
pylori(minus)stand
sfor
inactiv
esam
ples
c agaro
verla
yassayand(+)stand
sfor
activ
eextractsa
t50120583
gmL(minus)stand
sfor
inactiv
eextract
NAnot
applicableas
thereisn
orepo
rtin
theliterature
lowastStreptom
ycin
show
ed20
to23
mm
inhibitio
nzoneTh
eresto
fthe
studies
didno
treportthe
exactvalue
oftheinh
ibition
fortheirpo
sitivec
ontro
ls
Evidence-Based Complementary and Alternative Medicine 9
In general although different studies used plant materialsfrom different sources and nonsimilar extraction methodsethyl acetate and hexane extracts appear to be the strongestantioxidant extracts from the P bleo leaves [8 25 37]Moreover this antioxidant capacity is strongly associatedwith the total phenolic compounds and flavonoid content ofthe plant leaves [25 37 58] The above studies suggest thatP bleo has antioxidant properties which can be one of thepossible reasons for its traditional usage for detoxificationand prevention of cancer
343 Antimicrobial Properties P bleo has been shown topossess antibacterial antiviral and antifungal properties invitro Table 8 shows the effect of P bleo extracts on selectedbacteria and fungi As can be seen the methanol andhexane extracts demonstrated great antibacterial activitiesagainst Salmonella choleraesuis and Pseudomonas aeruginosaIn addition its dichloromethane extract showed promisingantibacterial effect againstMethicillin resistant Staphylococcusaureus [8 38] All of the mentioned bacteria are amongthe main causes of nosocomial infections and they havebeen developing antibiotic resistance [59ndash61] Therefore thepotential antibacterial activity of P bleo needs to be furtherinvestigated to identify the lead(s) antibacterial compo-nent(s)
The antifungal activity of the water and methanol extractof P bleo leaves against Cladosporium cucumerinum a plantpathogenic fungus has been reported [43] but they were notactive against Candida albicans a common human pathogen[42 43]
The antiviral properties of the water and methanolextracts of P bleo leaves were evaluated against HerpesSimplex Virus-I (HSV-1) andHuman Immunodeficiency Virus(HIV) by Matsuse et al [62] Both of the extracts demon-strated anti-HIV activity However the result of this studywas not promising because of the low selectivity index of094 Besides in another study by Hattori et al [63] the sameextracts did not demonstrate any antiviral activity againstHSV-1 In general the available data on the antiviral activityof P bleo is neither sufficient nor conclusive Thereforefurther research needs to be carried out
344 Antiparasitic Properties The only antiparasitic inves-tigation on P bleo was reported by Marston et al [52] Intheir study the chloroform methanol and water extractsof this plant did not exert any antiparasitic activity againstschistosomiasis
345 Neutralizing Snake Venom Otero et al [33] evaluatedthe neutralizing effect of the ethanol extract of P bleo onhemorrhagic activity of ldquoBothrops atrox venomrdquo in miceThisextract did not show any neutralizing effect against the testedvenom
346 Antinociceptive Properties Wahab et al [35] evaluatedthe antinociceptive activity of the ethanol extract and itsfractions using two in vivo analgesic models peripheralformalin-induced licking and acetic acid-induced abdominal
writhing They showed that the ethanol extract hexanefraction dichloromethane fraction and ethyl acetate fractionof P bleo had moderate antinociceptive effects However nocompound was identified in their study
35 Toxicity Studies Acute toxicity effect of the leaversquosextracts of P bleo was evaluated by in vitro and in vivostudies Er et al [32] showed that the water extract may formmutagenic compound(s) upon metabolization by the liverenzymes in vitro In another study by Gupta et al [22] themethanol extract of the whole plant had moderate toxicity inbrine shrimp toxicity assay (LD
5077 ppm) In the only in vivo
study by Sim et al [31] the methanol extract did not have anytoxicity effect on ICR mice (LD
50gt 2500mgkg) Although
animalmodels have around 70ndash80 predictability for humantoxicities [64 65] the long term toxicity and themutagenicityof metabolites of P bleo should be further investigated
4 Conclusion
A comprehensive review on Pereskia bleo has been presentedIt provides an overview of the botanical characteristics tra-ditional usage phytoconstituents pharmacological activitiesand safety of P bleo The current review highlights theassociation between the traditional usage of the plant andthe reported anticancer antibacterial and antinociceptiveeffects tested in different studies Although P bleo has beentraditionally used for a variety of therapeutic and prophy-lactic purposes only a few of them has been investigatedHence more research is warranted to further study itsbiological activities and chemical properties to understandits traditional usage and to develop novel therapeuticsUnderstanding the traditional uses knowing the availablescientific evidences and identifying the gaps in research willallow the proper translation of promising research results intoa safe and efficacious usage of herbal medicine and discoveryof new therapeutics It will also assist in setting appropriatepolicy and guidelines in the usage of herbal medicine
Conflict of Interests
All authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgments
Funding from the National University of Singapore (NUS)research Grant (R-148-000-137-112 to KHL) and LeewardPacific Pte Ltd (R-148-000-140-592 to KHL) and researchscholarship from the Singapore International GraduateAward (SINGA SZ) are acknowledged
References
[1] C Wiart Medicinal Plants of Asia and the Pacific Drugs of theFuture World Scientific Singapore 2006
[2] N L Britton and J N Rose The Cactaceae Descriptions andIllustrations of Plants of the Cactus Family Dover PublicationsWashington DC USA 2009
10 Evidence-Based Complementary and Alternative Medicine
[3] E J Edwards and M J Donoghue ldquoPereskia and the origin ofthe cactus life-formrdquo American Naturalist vol 167 no 6 pp777ndash793 2006
[4] E J Edwards R Nyffeler and M J Donoghue ldquoBasal cactusphylogeny implications of Pereskia (Cactaceae) paraphyly forthe transition to the cactus life formrdquo American Journal ofBotany vol 92 no 7 pp 1177ndash1188 2005
[5] R M Ogburn and E J Edwards ldquoAnatomical variation in Cac-taceae and relatives trait lability and evolutionary innovationrdquoAmerican Journal of Botany vol 96 no 2 pp 391ndash408 2009
[6] CM Boo C LOu-Yang andKOmar-Hor 1001Garden Plantsin Singapore National Parks Board Singapore 2nd edition2007
[7] Singapore Npark Board NParks FloraampFouna web 2010httpsflorafaunawebnparksgovsgSpecial-Pagesplant-detailaspxid=2324
[8] S I A Wahab A B Abdul S M Mohan A S Al-Zubairi MM Elhassan andMY Ibrahim ldquoBiological activities ofPereskiableo extractsrdquo International Journal of Pharmacology vol 5 no1 pp 71ndash75 2009
[9] R T Barcenas C Yesson and J A Hawkins ldquoMolecular sys-tematics of the CactaceaerdquoCladistics vol 27 no 5 pp 470ndash4892011
[10] K Y Chong H T Tan and R T Corlett A Checklist of theTotal Vascular Plant Flora of Singapore Native Naturalised andCultivated Species Raffles Museum of Biodiversity ResearchNational University of Singapore Singapore 2009 httprmbrnusedusgraffles museum pubflora of singapore tcpdf
[11] A M Sri Nurestri K S Sim and A W Norhanom ldquoPhy-tochemical and cytotoxic investigations of Pereskia grandifoliaHaw (Cactaceae) leavesrdquo Journal of Biological Sciences vol 9no 5 pp 488ndash493 2009
[12] E Anderson The Cactus Family pp 566ndash568 Timber PressPuritana Ore USA 1st edition 2001
[13] R P Wunderlin and B F Hansen ldquoAtlas of Florida VascularPlantsrdquo 2008 httpwwwplantatlasusfedu
[14] N P Taylor D Zappi P Braun and M Machado ldquoPereskiaaculeata Iucn Red List of Threatened Species Version 2013 2rdquo2013 httpwwwiucnredlistorg
[15] E Pooley A Field Guide to Wild Flowers KwaZulu Natal and theEastern Region Natal Flora Publications Trust Durban SouthAfrica 1999
[16] A G I Natural Heritage Trust ldquoWeedManagementGuide Leafcactus Pereskia aculeatardquo 2003 httpwwwenvironmentgovaubiodiversityinvasiveweedspublicationsguidelinesalertpubsp-aculeatapdf
[18] B E Leuenberger ldquoPereskia Maihuenia and Blossfeldia-taxonomic history updates and notesrdquo Haseltonia no 14 pp54ndash93 2008
[19] J Nugent ldquoPermaculture Plants agaves and cactirdquo 2007 httpbooksgooglecomsgbooksid=YVwMM2OdO34Campq=Pereskia+bleov=snippetampq=Pereskia20bleoampf=false
[20] B E Leuenberger ldquoHumboldt amp Bonplandrsquos Cactaceae in theherbaria at Paris and Berlinrdquo Willdenowia vol 32 pp 137ndash1532002
[21] KA LiamasTropical Flowering Plants AGuide to Identificationand Cultivation Timber Press Portland Ore USA 2003
[22] M P Gupta A Monge G A Karikas et al ldquoScreening of Pana-manian medicinal plants for brine shrimp toxicity crown
gall tumor inhibition cytotoxicity and DNA intercalationrdquoPharmaceutical Biology vol 34 no 1 pp 19ndash27 1996
[23] C C Kazama D T Uchida K N Canzi et al ldquoInvolvementof arginine-vasopressin in the diuretic and hypotensive effectsof Pereskia grandifoliaHaw (Cactaceae)rdquo Journal of Ethnophar-macology vol 144 no 1 pp 86ndash93 2012
[25] K S Sim A M Sri Nurestri and A W Norhanom ldquoPhenoliccontent and antioxidant activity of crude and fractionatedextracts of Pereskia bleo (Kunth) DC (Cactaceae)rdquo AfricanJournal of Pharmacy and Pharmacology vol 4 no 5 pp 193ndash201 2010
[26] EMurillo A JMelendez-Martınez and F Portugal ldquoScreeningof vegetables and fruits from Panama for rich sources of luteinand zeaxanthinrdquo Food Chemistry vol 122 no 1 pp 167ndash1722010
[27] K Hostettmann A Marston M Maillard and M HamburgerPhytochemistry of Plants Used in Traditional Medicine pp 373ndash376 Oxford University Press Oxford UK 1995
[28] S N A Malek S K Shin N A Wahab and H Yaacob ldquoCyto-toxic components of Pereskia bleo (Kunth) DC (Cactaceae)leavesrdquoMolecules vol 14 no 5 pp 1713ndash1724 2009
[29] M P Gupta A Correa DMireya et al ldquoMedicinal plant inven-tory of Kuna Indians part 1rdquo Journal of Ethnopharmacology vol40 no 2 pp 77ndash109 1993
[30] A Rahmat F P Saib and N A Buslima ldquoComparing theeffect of ficus benjamina extract and Pereskia saecnarosa extracton tthe level of micro and macro minerals in normal andinduced liver cancer ratsrdquo in Proceedings of the 4th InternationalConference on Biomedical Engineering in Vietnam pp 208ndash2121980
[31] K S Sim A M Sri Nurestri S K Sinniah K H Kim and AW Norhanom ldquoAcute oral toxicity of Pereskia bleo and Pereskiagrandifolia inmicerdquo PharmacognosyMagazine vol 6 no 21 pp67ndash70 2010
[32] H M Er E Cheng and A K Radhakrishnan ldquoAnti-proliferative and mutagenic activities of aqueous and methanolextracts of leaves from Pereskia bleo (Kunth) DC (Cactaceae)rdquoJournal of Ethnopharmacology vol 113 no 3 pp 448ndash456 2007
[33] R Otero V Nunez J Barona et al ldquoSnakebites and ethnob-otany in the northwest region of Colombia part III neutral-ization of the haemorrhagic effect of Bothrops atrox venomrdquoJournal of Ethnopharmacology vol 73 no 1-2 pp 233ndash2412000
[34] P W Doetsch J M Cassady and J L McLaughlin ldquoCac-tus alkaloids XL Identification of mescaline and other 120573-phenethylamines in Pereskia Pereskiopsis and Islaya by use offluorescamine conjugatesrdquo Journal of Chromatography A vol189 no 1 pp 79ndash85 1980
[35] I R A Wahab C C Guilhon P D Fernandes and F BoylanldquoAnti-nociceptive activity of Pereskia bleo Kunth (Cactaceae)leaves extractsrdquo Journal of Ethnopharmacology vol 144 no 3pp 741ndash746 2012
[36] S N AMalek N AWahabH Yaacob et al ldquoCytotoxic activityof Pereskia bleo (Cactaceae) against selected human cell linesrdquoInternational Journal of Cancer Research vol 4 no 1 pp 20ndash272008
Evidence-Based Complementary and Alternative Medicine 11
[37] B Hassanbaglou A A Hamid A Roheeyati et al ldquoAntioxidantactivity of different extracts from leaves of Pereskia bleo (Cac-taceae)rdquo Journal of Meidinal Plants Research vol 6 no 15 pp2932ndash2937 2012
[38] S I Abbdewahab N M Ain A B Abdul M M E Tahaand T A T Ibrahim ldquoEnergy-dispersive X-raymicroanalysis ofelementsrsquo content and antimicrobial properties of Pereskia bleoandGoniothalamus umbrosusrdquoAfrican Journal of Biotechnologyvol 8 no 10 pp 2375ndash2378 2009
[39] S Y Liew E J Stanbridge K Yusoff and N ShafeeldquoHypoxia affects cellular responses to plant extractsrdquo Journal ofEthnopharmacology vol 144 no 2 pp 453ndash456 2012
[40] M L Tan S F Sulaiman N Najimuddin M R Samian and TS T Muhammad ldquoMethanolic extract of Pereskia bleo (Kunth)DC (Cactaceae) induces apoptosis in breast carcinoma T47-D cell linerdquo Journal of Ethnopharmacology vol 96 no 1-2 pp287ndash294 2005
[41] K Philip S N A Malek W Sani et al ldquoAntimicrobial activityof some medicinal plants from Malaysiardquo American Journal ofApplied Sciences vol 6 no 8 pp 1613ndash1617 2009
[42] T Ruegg A I Calderon E F Queiroz et al ldquo3-farnesyl-2-hydroxybenzoic acid is a new anti-Helicobacter pylori com-pound from Piper multiplinerviumrdquo Journal of Ethnopharma-cology vol 103 no 3 pp 461ndash467 2006
[43] L Rahalison M Hamburger K Hostettmann et al ldquoScreeningfor antifungal activity of Panamanian plantsrdquo InternationalJournal of Pharmacognosy vol 31 no 1 pp 68ndash76 1993
[44] A P D Candolle ldquoPereskia bleo (Kunth) DCrdquo 2011 httpwwwtropicosorgName5100482
[47] M Gardener ldquoTropical plants library onlinerdquo 2014 httpmgonlinecomarticlesexoticsaspx
[48] S Kurt ldquoStem of P grandifoliardquo 2014 httpwwwbiolibde[49] NRCS ldquoNatural Resources and Conservation Service of
USDA Plant profile of P grandifolia Hawrdquo 2013 httpplantsusdagovcoreprofilesymbol=PEGR14
[50] D C Sanders A S Grayson andT JMonaco ldquoMineral contentof tomato (Lycopersicon esculentum) and four competing weedspeciesrdquoWeed Science vol 29 no 5 pp 590ndash593 1981
[51] J M Geleijnse J C Witteman A A Bak J H den Breeijenand D E Grobbee ldquoReduction in blood pressure with a lowsodium high potassium high magnesium salt in older subjectswith mild to moderate hypertensionrdquo British Medical Journalvol 309 no 6952 pp 436ndash440 1994
[52] A Marston G Dudan M P Gupta P N Solis M D Correaand K Hostettmann ldquoScreening of Panamanian plants formolluscicidal activityrdquo Pharmaceutical Biology vol 34 no 1 pp15ndash18 1996
[53] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999
[54] T Komiya M Kyohkon S Ohwaki et al ldquoPhytol inducesprogrammed cell death in human lymphoid leukemia Molt 4Bcellsrdquo International Journal of Molecular Medicine vol 4 no 4pp 377ndash380 1999
[55] M Gerber M C Boutron-Ruault S Hercberg E Riboli AScalbert and M H Siess ldquoFood and cancer state of the art
about the protective effect of fruits and vegetablesrdquo Bulletin duCancer vol 89 no 3 pp 293ndash312 2002
[56] V di Matteo and E Esposito ldquoBiochemical and therapeuticeffects of antioxidants in the treatment of Alzheimerrsquos diseaseParkinsonrsquos disease and amyotrophic lateral sclerosisrdquo CurrentDrug Targets-CNSampNeurological Disorders vol 2 no 2 pp 95ndash107 2003
[57] P Knekt R Jarvinen A Reunanen and J Maatela ldquoFlavonoidintake and coronary mortality in Finland a cohort studyrdquoBritish Medical Journal vol 312 no 7029 pp 478ndash481 1996
[58] R A Mustafa A Abdul Hamid S Mohamed and F A BakarldquoTotal phenolic compounds flavonoids and radical scavengingactivity of 21 selected tropical plantsrdquo Journal of Food Sciencevol 75 no 1 pp C28ndashC35 2010
[59] E B Breidenstein C de la Fuente-Nunez and R E HancockldquoPseudomonas aeruginosa all roads lead to resistancerdquo Trendsin Microbiology vol 19 no 8 pp 419ndash426 2011
[60] C Chu C-H ChiuW-YWu C-H Chu T-P Liu and J T OuldquoLarge drug resistance virulence plasmids of clinical isolates ofSalmonella enterica serovar Choleraesuisrdquo Antimicrobial Agentsand Chemotherapy vol 45 no 8 pp 2299ndash2303 2001
[61] K Hiramatsu H Hanaki T Ino K Yabuta T Oguri andF Tenover ldquoMethicillin-resistant Staphylococcus aureus clini-cal strain with reduced vancomycin susceptibilityrdquo Journal ofAntimicrobial Chemotherapy vol 40 no 1 pp 135ndash136 1997
[62] I TMatsuse Y A LimMHattori M Correa andM P GuptaldquoA search for anti-viral properties in Panamanian medicinalplants the effects on HIV and its essential enzymesrdquo Journal ofEthnopharmacology vol 64 no 1 pp 15ndash22 1998
[63] M Hattori T Nakabayashi Y A Lim et al ldquoInhibitory effectsof various Ayurvedic and Panamanian medicinal plants onthe infection of herpes simplex virus-1 in vitro and in vivordquoPhytotherapy Research vol 9 no 4 pp 270ndash276 1995
[64] I Kola and J Landis ldquoCan the pharmaceutical industry reduceattrition ratesrdquoNature Reviews Drug Discovery vol 3 no 8 pp711ndash716 2004
[65] H Olson G Betton D Robinson et al ldquoConcordance ofthe toxicity of pharmaceuticals in humans and in animalsrdquoRegulatory Toxicology and Pharmacology vol 32 no 1 pp 56ndash67 2000
11 Pereskia aculeata Mill Its common names are Barbadosgooseberry or lemon vine [12 13] and it is native to tropicalAmerica [14] This plant is a scrambling vine growing to theheight of 10m to a tree The stems reach 2-3 cm in diameterYounger stems have hooked thorns and older stems haveclusters of woody spines The leaves are 4ndash11 cm long and15ndash4 cm wide simple and deciduous in the dry season Theflowers are white cream or pinkish with 25ndash5 cm diameterand strongly scented This plant has translucent roundedwhite to pink berries which turn to yellow or orange withthe diameter of 2 cm upon ripeningThe fruits are edible andcontaining numerous small seeds They somewhat resemblethe gooseberry in appearance and are of excellent flavor[15 16] The leaves are also edible and are a popular vegetablein parts of the Brazilian state ofMinas Gerais under the nameof ora-pro-nobis [14]
12 Pereskia grandifolia Haw It is also known as rose cac-tus or Rhodocactus grandifolia This plant is native to theNortheastern Brazil restingas and is cultivated in tropicaland subtropical areas [7] It is a shrub or small tree 2ndash5mhigh with a grayish-brown trunk up to 20 cm in diameterThe spines range from black to brown and their numberat each areole gradually increases with age The new twigsmay be spineless while the trunk may have up to 90 spinesin areoles each 2ndash65 cm long The leaves vary in sizefrom 9 to 23 cm long and the shapes range from elliptic toovate and obovate-lanceolate Usually 10ndash15 flowers of denseinflorescence develop at the ends of stems but sometimesthere are 30 or more The flowers are pink-purple and looklike rosewith 3ndash5 cmdiameter [12]The leaves ofP grandifoliaare edible [11]
13 Pereskia bleo (Kunth) DC P bleo is also known as Cactusbleo and has been commonly used for a variety of medicinaland non-medicinal purposes in different countries [1 2]However to the best of our knowledge a comprehensivereview of P bleo is not available The objective of this paper isto provide a comprehensive review of the botanical character-istics traditional usage phytoconstituents pharmacologicalactivities and safety of P bleo Such information will serve asa useful resource for the proper usage of this plant and forfuture research
2 Method
Internet sources including MEDLINE (via Pubmed) Sciencedirect Scopus and Google scholar and China Journals Full-Text Database (via CNKI) were searched for publications onthis plant The following keywords were used Pereskia bleoPereskia panamensis Pereskia corrugata Rhodocactus cor-rugatus Rhodocactus bleo Cactus panamensis Cactus bleoSpinach cactus wax rose Perescia and Chinese rose Norestriction on the language and date of publication wasimplemented In addition available books and eBooks inthe National University of Singapore (NUS) libraries weremanually searched for the relevant information
3 Results and Discussion
31 Botanical Characteristics P bleo belongs to the orderof Caryophyllales Juss ex Bercht amp J Presl superorder ofCaryophyllanae Takht and subclass of Magnoliidae Novak exTakht It is in the Cactaceae family Peresioideae subfamilyand Pereskia Mill genus [44 45] In the International PlantNomenclature Index (IPNI) [46] its ID code is 273592-2and its basionym is Cactus bleo (Kunth) Basionym name isdefined as ldquopreviously published legitimate name-bringing orepithet-bringing synonym fromwhich a new name is formedfor a taxon of different rank or position taxon of differentrank or positionrdquo [17]The scientific and common names of Pbleo are listed in Table 2 This plant is also known as ldquoPokokJarumTujuh Bilahrdquo inMalay and ldquoCak Sing Camrdquo or ldquoQi XingZhen (七星针)rdquo in Chinese [8 40] Its Chinese name literallymeans ldquoseven stars needlerdquo [7]
P bleo originates from Mesoamerica (Panama) WesternSouth America (Columbia) [1 2 6 12] and is distributedin tropical and subtropical regions [1 2] It is a deciduousshrubby tree-like plant with a height of 06ndash8m The trunkreaches 10 cm in diameter and bears very large fascicle ofspines when it is young However the trunk becomes nakedwhen turning old Young branches are red and leafy andoften bear 5ndash7 black spines up to 1 cm in length The spinesreach 2 cm on the older stems The leaves are thin oblongto oblanceolate glossy and succulent 6ndash21 cm long and 2ndash7 cm wide [2] The flowers are orange-red and grouped in 2ndash4 terminally and laterally The fruits are yellow thick walledfleshy and glossy and look like conical berries at maturityup to 5 times 5 cm in size turbinate and containing 6ndash8mm indiameter dark brown or black color seeds [1 19 31] It can bepropagated by stem cutting or seeds [12]
This species was collected by Bonpland during Hum-boldtrsquos trip through the new world and was described andpublished by Kunth in 1823 [2] In some older books andherbaria it was confused with Pereskia grandifolia (P gran-difolia) [20] because both plants are vegetatively similar [31]In addition P bleo and P grandifolia are the only exceptionsof Pereskia which grow in areas receiving considerably highannual rainfall more than 187mm per wet month OtherPereskia species grow in dry areas [3] The two speciescan be distinguished by the leaves flowers and spines Pbleo has thinner corrugated leaves and orange-red flowerswith shorter spines compared to P grandifolia In contrast
Evidence-Based Complementary and Alternative Medicine 3
Common namesButarrar (Kuna Indian) [22]Cak Sing Cam Qi xing zhen (Chinese) [1 8 23]Chupa Chupa melon Najiı Najii De Culebra Naju de esoubas and Bleo de chupa (Spanish) [2 21 24]Perescia [7]Pokok Jarum Tujuh Bilah (Malay) [2 25]Rose cactus Bleo Chinese rose Spinach cactus wax rose and orange rose cactus (English) [1 6 7 21 24 26]
Table 3 Traditional usage and methods of preparation of P bleo
Purpose Method of preparation References
Detoxification and prevention of cancer Making tea by boiling the leaves andor the fruit and then drinking itwarm or cool [27ndash30]
Dietary purposes and health maintenance Eating the raw leaf flower and fruit [19 28]Health maintenance and revitalizing thebody
Making juice from the leaves and boiling in water and drinking everymorning [30]
To alleviate muscleache Making decoction from the leaves and then using as a warm bath formuscle ache [29]
To alleviate stomachache
Preparing ldquoina kuamakaletrdquo the inflorescence is mixed with theexcrements of red ants by using a special mortar and then moistenedwith water The resulted mass is moulded to oval shape objects whichare dried in sun When using the remedy these balls are rubbed in asmall container with a small amount of water
[29]
To treat hemorrhoid hypertensiondiabetes infections headache andinflammatory conditions (rheumatismand asthma)
No information is available in the literature [28 31 32]
To neutralize the effects of the snakebites No information is available in the literature [33]
P grandifolia has thicker uncorrugated leaves pink topurplish-pink flowers and longer but fewer spines on thestems [11] Figure 1 shows the photographs of different partsof P bleo and P grandifolia Although they are differentspecies anatomical similarities in these two species supportthe evolution theory for cactus family [18]
32 Traditional Usage P bleo has been used for various pur-poses In some areas it is used as a food spice [1 7] Thisplant has been eaten raw as vegetables by some people inMalaysia and China or taken as a concoction brewed fromfresh leaves [19 36] In addition it is taken for detoxificationand revitalizing the body [27 28 40] Its fruit is consumedby some ethnic groups in Panama as a wild fruit [26] Theleaves of P bleo have been traditionally used to treat can-cer hemorrhoid hypertension diabetes [32 40] infectionsgastric pain headache ulcer and inflammatory conditions
like rheumatism and asthma [28 31] Indigenous Colombianshave used P bleo to neutralize the effects of snakebites [33]to relax spastic muscles and to alleviate muscle aches [29]Apart from dietary andmedicinal uses this plant is a suitablebarrier hedge because of its sharp spines strong stem andinsect repellant properties [21] In Central America KunaIndians used the crushed leaves to clarify drinking water[12] Different methods of preparation have been reportedfor the plant It is usually taken raw or as a decoction of itsfresh leaves Table 3 shows the traditional usage and differentpreparation methods of P bleo To the best of our knowledgeinformation on the specific preparation methods for some ofthe indicated traditional usages is not available
33 Phytochemistry The leaves are the most commonly usedpart of P bleo in traditional medicine Hence they have beenmore studied compared to the other plant parts So far 20
4 Evidence-Based Complementary and Alternative Medicine
Table 4 Reported phytoconstituents in the leaves and fruits of P bleo
Plant part Class of the constituents Constituents Reference
Fruit Carotenoids Lutein (120573e-carotene-331015840-diol) [26 37]Zeaxanthin (120573120573-carotene-331015840-diol)
Table 5 Percentage ( ww) of mineral contents in the leaves of Pbleo [38]
Mineral elements Percentage weight ()Carbon 506Oxygen 354Magnesium 04Phosphorus 04Sulfur 15Chlorine 12Potassium 102Aluminium NDlowast
Calcium 03Silicon NDFerrum (Iron) NDlowastND not detected
phytoconstituents have been reported in the leaves and twocomponents from the fruit as shown in Table 4 These com-ponents include alkaloids fatty acids glycosides lactonesphenolic sterol terpenoid and carotenoid compounds Themajor isolated component from P bleo leaves is phytol [27]In addition Doetsch et al [34] reported the isolation ofthree alkaloids namely 34-dimethoxy-120573-phenethylamine(mescaline) 3-methoxytyramine and tyramine from theleaves of this plant Vitamin E (120572-tocopherol) [36 37] which
is well known for its antioxidant properties 24-ditert-butylphenol and dihydroactinidiolide were isolated throughbioassay-guided fractionation by Malek et al [36] Murillo etal [26] analyzed the fruit of P bleo for lutein and zeaxanthincontents The total carotenoid content of the fruit was foundto be 133 120583gg making P bleo fruit a high carotenoid foodsource among the wild fruits in Panama
Themineral content of the leaves was also investigated byusing energy-dispersive X-ray microanalysis Table 5 showsthe weight percentage of the minerals reported by Abbde-wahab et al [38] As can be seen P bleo leaves are richin potassium (1016) This is more than two times of thepotassium content of tomato (45) a vegetable known tobe high in potassium [50] It has been shown that a highpotassium diet has an important role in lowering bloodpressure [51] Therefore it might be one of the possiblereasons for the traditional usage of P bleo as a treatment forhypertension [31]
34 Pharmacological Properties Pharmacological evaluationof plants is based on their traditional uses Cancer is oneof the main causes of mortality and morbidity Since Pbleo is traditionally used to prevent and treat cancer [2830 40] it has been most studied for its antiproliferativeand cancer protective properties [8 22 28 32 36 39 40]This is followed by investigations of its antimicrobial andantiparasitic effects in vitro [8 38 41ndash43 52] The snake
Evidence-Based Complementary and Alternative Medicine 5
(a) (b)
(c) (d)
(e) (f)
Figure 1 Photographs of different plant parts of P bleo and P grandifolia (a) Flower of P bleo (b) lower of P grandifolia [47] (c) stem andspines of P bleo (d) stem and spines of P grandifolia [48] (e) ripe fruits and seeds of P bleo and (f) ripe fruits and seeds of P grandifolia [49]
venom neutralizing properties [33] antinociceptive effects[35] and toxicity [22 31] of this plant have been evaluatedthrough in vivo studies
341 Antiproliferative Properties The effects of different Pbleo extracts have been reported on various cell lines in vitroThe crude methanol extract and its ethyl acetate fraction had
significant cytotoxic effects against human nasopharyngealepidermoid carcinoma cell line (KB) [36] In addition theethyl acetate fraction was more active than the methanolextract against human colon carcinoma (HCT116) and hor-mone dependent breast carcinoma cell lines (MCF7) [36]Table 6 shows the reported IC
50values (120583gmL) for the
antiproliferative effects of P bleo extracts and fractions
6 Evidence-Based Complementary and Alternative Medicine
Table6IC
50values
(120583gmL)
ofPbleo
leafextractsandfractio
nson
different
celllin
es
Cellline
Extractsandfractio
ns(IC 5
0120583gmL)
Positivec
ontro
l(IC
50120583
gmL)
Negativec
ontro
lRe
ferences
Methano
lWater
Hexane
Dichlorom
ethane
Ethylacetate
4T1
gt50
gt50
NA
NA
NA
Cisplatin
(NA)
NA
[32]
CasK
i40
5mdash
895
NA
58Doxorub
icin
(6times10minus3)
NA
[36]
CEM-ss
mdashNA
mdashmdash
mdashNA
VC[8]
HT2
9andHCT
116gt30
NA
gt30
gt30
gt30
NA
VC[8]
416
mdash675
NA
22Doxorub
icin
(36times10minus1)
NA
[36]
KB65
mdash28
NA
45
Doxorub
icin
(12times10minus2)
NA
[36]
MCF
-7gt30
NA
gt30
gt30
gt30
NA
VC[8]
39mdash
25NA
28Doxorub
icin
(75times10minus2)
NA
[36]
MRC
-5mdash
mdashmdash
NA
mdashDoxorub
icin
(55times10minus1)
NA
[36]
NIH
3T3
ge200
ge200
NA
NA
NA
Cisplatin
NA
[32]
Saos-2
mdashNA
NA
NA
NA
Cisplatin
NA
[39]
T-47D
2NA
NA
NA
NA
DNaseI
VC[40]
V79
mdashNA
NA
NA
NA
Nitracrin
eVC
[22]
IC5050
ofmaxim
umcellinhibitio
nIC
50lt20120583gmLisconsidered
activ
e100gtIC
50gt20120583gmLisrelativ
elyactiv
eandIC
50gt100isno
tactive[8]
(mdash)no
activ
ity
4T1mou
semam
marycancer
celllin
eCa
sKihu
man
cervicalcarcinom
acelllin
eCE
M-sshu
man
T-4lymph
oblasto
idcelllin
eHT2
9andHCT
116hum
ancoloncarcinom
acelllin
eKB
hum
annasoph
aryn
geal
epidermoidcarcinom
acelllin
eMCF
-7h
ormon
edependent
breastcarcinom
acelllin
eMRC
-5n
ormalhu
man
fibroblastcelllinesN
IH3T3
normalmou
sefib
roblastcelllineSaos-2hum
anosteosarcomacell
lineT-47Dhum
anbreastcarcinom
acelllineV79C
hinese
hamste
rlun
gfib
roblasts
NAnot
available
VCvehiclecontrol
Evidence-Based Complementary and Alternative Medicine 7
Table 7 Reported IC50 values (120583gmL) of selected P bleo phytoconstituents on human cell lines [28]
Compound IC50 (120583gmL) of different cell linesKB MCF7 CasKi HCT 116 A549 MRC-5
Dihydroactinidiolide 67 30 40 5 97 913120573-sitosterol gt100 72 62 gt100 78 gt10024-ditertbutylphenol 081 575 45 29 6 20120572-tocopherol 8 75 6 31 6 305Phytol 71 34 18 100 31 741Mixture of sterols gt100 gt100 gt100 gt100 gt100 gt100Doxorubicin 13 times 10minus2 76 times 10minus2 60 times 10minus3 36 times 10minus1 22 times 10minus1 55 times 10minus1
A549 human lung carcinoma cell line CasKi human cervical carcinoma cell Line HCT116 human colon carcinoma cell Line KB human nasopharyngealepidermoid carcinoma cell Line MCF-7 hormone dependent breast carcinoma cell Line MRC-5 normal human fibroblast cell Lines
Gupta et al [22] reported high tumor inhibition activityin ldquopotato disc inhibition assayrdquo using crown gall tumors(LC5077 ppm)Their result was accompanied by a significant
DNA peak reduction in the DNA intercalation test for themethanol extract of the whole plant
To date no report is available on the in vivo antiprolifer-ative activities of P bleo
(1) Cytotoxic Components Some of the cytotoxic componentsin P bleo have been reported Table 7 shows the reported IC
50
(120583gmL) values of these components in the different humancell lines The effects of these compounds and the mixture ofthe isolated sterols were not as high as doxorubicin that isa chemotherapy drug [28] In another study phytol isolatedfrom P bleo leaves was found to have a significant antitumoractivity against some mouse cancer cell lines [36]
(2) Proposed Antiproliferative Mechanism The antiprolifera-tive activity of the methanol extract of P bleo against humanbreast carcinoma cell line (T-47D) was found to be apoptoticin nature through the activation of caspase-3 and c-mycpathways [40] Caspase-3 and c-myc are frequently activateddeath proteases which catalyze the specific cleavage of manykey cellular proteins They are also essential for normaldevelopment of the tissues as well as apoptosis in the tissuesand cell types [53] Komiya et al [54] reported the inductionof apoptosis as a mechanism of action for cytotoxic activityof phytol DNA intercalation is another proposedmechanismof antiproliferative activity for P bleo [22] However in somestudies P bleo did not show appreciable cytotoxic effect [32]Differences in the sources of plants extractionmethods assaymethods and cell lines can be the possible reasons for thesediscrepancies On the other hand P bleo may contain someprodrugs which are metabolized to the active metabolitesTherefore further studies are needed to better understand itsantiproliferative activity
Apart from the cytotoxic activities against cancer celllines crudemethanol extract and its fractions (hexane waterand ethyl acetate) did not show any cytotoxicity to the normalhuman fibroblast cell lines MRC-5 [36]
342 Antioxidant Activity The adverse effects of oxida-tive stress on human health have become a serious issueOxidative stress causes production of free radicals in thebody that facilitate the development of degenerative diseasessuch as cardiovascular diseases cancers neurodegenerativedisorders [55] Alzheimerrsquos and inflammatory diseases [56]One solution to this problem is to supplement the diet withantioxidant compounds found in natural plant sources [57]Hence in the literature the antioxidant effects of P bleo wereevaluated using different assays as follows
22-Diphenyl-1-picrylhydrazyl Hydrate (DPPH) Assay Themethanol dichloromethane ethyl acetate and hexaneextracts of P bleo leaves were tested [8 25] The hexaneextract exhibited the most effective radical scavengingactivity (EC
50210 120583gmL) followed by the ethyl acetate
extract (EC50
225120583gmL) This spectrophotometric assayuses a stable radical 221015840-diphenylpicrylhydrazyl (DPPH) asa reagent [8 25]
Ferric Reducing Antioxidant Potential Assay (FRAP) Thehexane water and methanol extracts of P bleo leaves werefound to reduce Fe3+ferric cyanide complex to the ferrousform Although the reduction was statistically significant itwas not more than ascorbic acid (vitamin C) and butylatedhydroxyanisole (BHA) as positive controls [25] Hassanba-glou et al [37] compared the antioxidant activity of the ethylacetate extract with that of hexane ethanol and methanolextracts They showed that the ethyl acetate extract hadsignificantly higher antioxidant properties compared to therest of the tested extracts FRAP measures the ability of testsamples to reduce ferric ion to the ferrous form of TPTZ(246-tripyridyl-s-triazine)
120573-Carotene-Linoleic Bleaching AssayThe ethyl acetate extractof P bleo demonstrated the strongest antioxidant activityfollowed by the methanol extract reported by Sim et al [25]In this assay the linoleate free radicals formed during thereaction are neutralized by antioxidants
8 Evidence-Based Complementary and Alternative Medicine
Table8Re
ported
effectsof
Pbleo
extractson
theg
rowth
ofselected
bacteriaandfung
i
Organism
Antibacteria
land
antifun
galeffectof
thee
xtracts
Positivec
ontro
lRe
ferences
Methano
lWater
Hexane
Dichloroethane
Ethylacetate
Chloroform
Bacillussubtilisa
minusNA
minusminus
minusNA
Streptom
ycinlowast
[8]
minusminus
minusNA
minusNA
Gentamicinampicillin
[41]
NA
NA
minusminus
NA
NA
Streptom
ycin
[38]
Escherich
iacolib
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Escherich
iacolia
minusminus
minusNA
minusNA
Gentamicinampicillin
[41]
Helicobacterpylorib
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Klebsiella
pneumoniaeb
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Methicillin
resistant
Staphylococcus
aureus
aminus
NA
minus++
+minus
NA
Streptom
ycinlowast
[8]
NA
NA
minus++
NA
NA
Streptom
ycin
[38]
Mycobacteriu
msm
egmatisb
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Pseudomonas
aeruginosa
a++
NA
+++
++
NA
Streptom
ycin
[8]
+minus
minusNA
+NA
Gentamicinampicillin
[41]
NA
NA
+++
+NA
NA
Streptom
ycinlowast
[38]
Pseudomonas
aeruginosa
bminus
NA
NA
minusNA
NA
Streptom
ycin
[42]
Salm
onellacholeraesuisa
++NA
+++
minusminus
NA
Streptom
ycinlowast
[8]
NA
NA
+++
minusNA
NA
Streptom
ycin
[38]
Staphylococcus
aureus
bminus
NA
NA
minusNA
NA
Streptom
ycin
[42]
Staphylococcus
aureus
aminus
minusminus
NA
minusNA
Gentamicinampicillin
[41]
Cand
idaalbicans
cminus
minusNA
NA
NA
minusProp
icon
azolemicon
azole
[43]
Cand
idaalbicans
bminus
NA
NA
minusNA
NA
Amph
otericin
B[42]
Cladosporiu
mcucumerinum
c+
+NA
NA
NA
+Prop
icon
azolemicon
azole
[43]
a Thes
creening
fora
ntibacteria
leffectwas
carriedou
tbyd
eterminingthez
oneo
finh
ibition
usingpaperd
isc+
stand
sfor
activ
itybetween6ndash
9mm+
+sta
ndsfor
activ
itybetween9ndash
14mm+
++stands
fora
ctivity
morethan14mm
[38]
b (+)
stand
sfor
activ
ityat100120583
gmLforE
coliS
aureusK
pneum
oniaeMsmegmatis
CalbicanceP
aeruginosa
andat125120583gmLforH
pylori(minus)stand
sfor
inactiv
esam
ples
c agaro
verla
yassayand(+)stand
sfor
activ
eextractsa
t50120583
gmL(minus)stand
sfor
inactiv
eextract
NAnot
applicableas
thereisn
orepo
rtin
theliterature
lowastStreptom
ycin
show
ed20
to23
mm
inhibitio
nzoneTh
eresto
fthe
studies
didno
treportthe
exactvalue
oftheinh
ibition
fortheirpo
sitivec
ontro
ls
Evidence-Based Complementary and Alternative Medicine 9
In general although different studies used plant materialsfrom different sources and nonsimilar extraction methodsethyl acetate and hexane extracts appear to be the strongestantioxidant extracts from the P bleo leaves [8 25 37]Moreover this antioxidant capacity is strongly associatedwith the total phenolic compounds and flavonoid content ofthe plant leaves [25 37 58] The above studies suggest thatP bleo has antioxidant properties which can be one of thepossible reasons for its traditional usage for detoxificationand prevention of cancer
343 Antimicrobial Properties P bleo has been shown topossess antibacterial antiviral and antifungal properties invitro Table 8 shows the effect of P bleo extracts on selectedbacteria and fungi As can be seen the methanol andhexane extracts demonstrated great antibacterial activitiesagainst Salmonella choleraesuis and Pseudomonas aeruginosaIn addition its dichloromethane extract showed promisingantibacterial effect againstMethicillin resistant Staphylococcusaureus [8 38] All of the mentioned bacteria are amongthe main causes of nosocomial infections and they havebeen developing antibiotic resistance [59ndash61] Therefore thepotential antibacterial activity of P bleo needs to be furtherinvestigated to identify the lead(s) antibacterial compo-nent(s)
The antifungal activity of the water and methanol extractof P bleo leaves against Cladosporium cucumerinum a plantpathogenic fungus has been reported [43] but they were notactive against Candida albicans a common human pathogen[42 43]
The antiviral properties of the water and methanolextracts of P bleo leaves were evaluated against HerpesSimplex Virus-I (HSV-1) andHuman Immunodeficiency Virus(HIV) by Matsuse et al [62] Both of the extracts demon-strated anti-HIV activity However the result of this studywas not promising because of the low selectivity index of094 Besides in another study by Hattori et al [63] the sameextracts did not demonstrate any antiviral activity againstHSV-1 In general the available data on the antiviral activityof P bleo is neither sufficient nor conclusive Thereforefurther research needs to be carried out
344 Antiparasitic Properties The only antiparasitic inves-tigation on P bleo was reported by Marston et al [52] Intheir study the chloroform methanol and water extractsof this plant did not exert any antiparasitic activity againstschistosomiasis
345 Neutralizing Snake Venom Otero et al [33] evaluatedthe neutralizing effect of the ethanol extract of P bleo onhemorrhagic activity of ldquoBothrops atrox venomrdquo in miceThisextract did not show any neutralizing effect against the testedvenom
346 Antinociceptive Properties Wahab et al [35] evaluatedthe antinociceptive activity of the ethanol extract and itsfractions using two in vivo analgesic models peripheralformalin-induced licking and acetic acid-induced abdominal
writhing They showed that the ethanol extract hexanefraction dichloromethane fraction and ethyl acetate fractionof P bleo had moderate antinociceptive effects However nocompound was identified in their study
35 Toxicity Studies Acute toxicity effect of the leaversquosextracts of P bleo was evaluated by in vitro and in vivostudies Er et al [32] showed that the water extract may formmutagenic compound(s) upon metabolization by the liverenzymes in vitro In another study by Gupta et al [22] themethanol extract of the whole plant had moderate toxicity inbrine shrimp toxicity assay (LD
5077 ppm) In the only in vivo
study by Sim et al [31] the methanol extract did not have anytoxicity effect on ICR mice (LD
50gt 2500mgkg) Although
animalmodels have around 70ndash80 predictability for humantoxicities [64 65] the long term toxicity and themutagenicityof metabolites of P bleo should be further investigated
4 Conclusion
A comprehensive review on Pereskia bleo has been presentedIt provides an overview of the botanical characteristics tra-ditional usage phytoconstituents pharmacological activitiesand safety of P bleo The current review highlights theassociation between the traditional usage of the plant andthe reported anticancer antibacterial and antinociceptiveeffects tested in different studies Although P bleo has beentraditionally used for a variety of therapeutic and prophy-lactic purposes only a few of them has been investigatedHence more research is warranted to further study itsbiological activities and chemical properties to understandits traditional usage and to develop novel therapeuticsUnderstanding the traditional uses knowing the availablescientific evidences and identifying the gaps in research willallow the proper translation of promising research results intoa safe and efficacious usage of herbal medicine and discoveryof new therapeutics It will also assist in setting appropriatepolicy and guidelines in the usage of herbal medicine
Conflict of Interests
All authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgments
Funding from the National University of Singapore (NUS)research Grant (R-148-000-137-112 to KHL) and LeewardPacific Pte Ltd (R-148-000-140-592 to KHL) and researchscholarship from the Singapore International GraduateAward (SINGA SZ) are acknowledged
References
[1] C Wiart Medicinal Plants of Asia and the Pacific Drugs of theFuture World Scientific Singapore 2006
[2] N L Britton and J N Rose The Cactaceae Descriptions andIllustrations of Plants of the Cactus Family Dover PublicationsWashington DC USA 2009
10 Evidence-Based Complementary and Alternative Medicine
[3] E J Edwards and M J Donoghue ldquoPereskia and the origin ofthe cactus life-formrdquo American Naturalist vol 167 no 6 pp777ndash793 2006
[4] E J Edwards R Nyffeler and M J Donoghue ldquoBasal cactusphylogeny implications of Pereskia (Cactaceae) paraphyly forthe transition to the cactus life formrdquo American Journal ofBotany vol 92 no 7 pp 1177ndash1188 2005
[5] R M Ogburn and E J Edwards ldquoAnatomical variation in Cac-taceae and relatives trait lability and evolutionary innovationrdquoAmerican Journal of Botany vol 96 no 2 pp 391ndash408 2009
[6] CM Boo C LOu-Yang andKOmar-Hor 1001Garden Plantsin Singapore National Parks Board Singapore 2nd edition2007
[7] Singapore Npark Board NParks FloraampFouna web 2010httpsflorafaunawebnparksgovsgSpecial-Pagesplant-detailaspxid=2324
[8] S I A Wahab A B Abdul S M Mohan A S Al-Zubairi MM Elhassan andMY Ibrahim ldquoBiological activities ofPereskiableo extractsrdquo International Journal of Pharmacology vol 5 no1 pp 71ndash75 2009
[9] R T Barcenas C Yesson and J A Hawkins ldquoMolecular sys-tematics of the CactaceaerdquoCladistics vol 27 no 5 pp 470ndash4892011
[10] K Y Chong H T Tan and R T Corlett A Checklist of theTotal Vascular Plant Flora of Singapore Native Naturalised andCultivated Species Raffles Museum of Biodiversity ResearchNational University of Singapore Singapore 2009 httprmbrnusedusgraffles museum pubflora of singapore tcpdf
[11] A M Sri Nurestri K S Sim and A W Norhanom ldquoPhy-tochemical and cytotoxic investigations of Pereskia grandifoliaHaw (Cactaceae) leavesrdquo Journal of Biological Sciences vol 9no 5 pp 488ndash493 2009
[12] E Anderson The Cactus Family pp 566ndash568 Timber PressPuritana Ore USA 1st edition 2001
[13] R P Wunderlin and B F Hansen ldquoAtlas of Florida VascularPlantsrdquo 2008 httpwwwplantatlasusfedu
[14] N P Taylor D Zappi P Braun and M Machado ldquoPereskiaaculeata Iucn Red List of Threatened Species Version 2013 2rdquo2013 httpwwwiucnredlistorg
[15] E Pooley A Field Guide to Wild Flowers KwaZulu Natal and theEastern Region Natal Flora Publications Trust Durban SouthAfrica 1999
[16] A G I Natural Heritage Trust ldquoWeedManagementGuide Leafcactus Pereskia aculeatardquo 2003 httpwwwenvironmentgovaubiodiversityinvasiveweedspublicationsguidelinesalertpubsp-aculeatapdf
[18] B E Leuenberger ldquoPereskia Maihuenia and Blossfeldia-taxonomic history updates and notesrdquo Haseltonia no 14 pp54ndash93 2008
[19] J Nugent ldquoPermaculture Plants agaves and cactirdquo 2007 httpbooksgooglecomsgbooksid=YVwMM2OdO34Campq=Pereskia+bleov=snippetampq=Pereskia20bleoampf=false
[20] B E Leuenberger ldquoHumboldt amp Bonplandrsquos Cactaceae in theherbaria at Paris and Berlinrdquo Willdenowia vol 32 pp 137ndash1532002
[21] KA LiamasTropical Flowering Plants AGuide to Identificationand Cultivation Timber Press Portland Ore USA 2003
[22] M P Gupta A Monge G A Karikas et al ldquoScreening of Pana-manian medicinal plants for brine shrimp toxicity crown
gall tumor inhibition cytotoxicity and DNA intercalationrdquoPharmaceutical Biology vol 34 no 1 pp 19ndash27 1996
[23] C C Kazama D T Uchida K N Canzi et al ldquoInvolvementof arginine-vasopressin in the diuretic and hypotensive effectsof Pereskia grandifoliaHaw (Cactaceae)rdquo Journal of Ethnophar-macology vol 144 no 1 pp 86ndash93 2012
[25] K S Sim A M Sri Nurestri and A W Norhanom ldquoPhenoliccontent and antioxidant activity of crude and fractionatedextracts of Pereskia bleo (Kunth) DC (Cactaceae)rdquo AfricanJournal of Pharmacy and Pharmacology vol 4 no 5 pp 193ndash201 2010
[26] EMurillo A JMelendez-Martınez and F Portugal ldquoScreeningof vegetables and fruits from Panama for rich sources of luteinand zeaxanthinrdquo Food Chemistry vol 122 no 1 pp 167ndash1722010
[27] K Hostettmann A Marston M Maillard and M HamburgerPhytochemistry of Plants Used in Traditional Medicine pp 373ndash376 Oxford University Press Oxford UK 1995
[28] S N A Malek S K Shin N A Wahab and H Yaacob ldquoCyto-toxic components of Pereskia bleo (Kunth) DC (Cactaceae)leavesrdquoMolecules vol 14 no 5 pp 1713ndash1724 2009
[29] M P Gupta A Correa DMireya et al ldquoMedicinal plant inven-tory of Kuna Indians part 1rdquo Journal of Ethnopharmacology vol40 no 2 pp 77ndash109 1993
[30] A Rahmat F P Saib and N A Buslima ldquoComparing theeffect of ficus benjamina extract and Pereskia saecnarosa extracton tthe level of micro and macro minerals in normal andinduced liver cancer ratsrdquo in Proceedings of the 4th InternationalConference on Biomedical Engineering in Vietnam pp 208ndash2121980
[31] K S Sim A M Sri Nurestri S K Sinniah K H Kim and AW Norhanom ldquoAcute oral toxicity of Pereskia bleo and Pereskiagrandifolia inmicerdquo PharmacognosyMagazine vol 6 no 21 pp67ndash70 2010
[32] H M Er E Cheng and A K Radhakrishnan ldquoAnti-proliferative and mutagenic activities of aqueous and methanolextracts of leaves from Pereskia bleo (Kunth) DC (Cactaceae)rdquoJournal of Ethnopharmacology vol 113 no 3 pp 448ndash456 2007
[33] R Otero V Nunez J Barona et al ldquoSnakebites and ethnob-otany in the northwest region of Colombia part III neutral-ization of the haemorrhagic effect of Bothrops atrox venomrdquoJournal of Ethnopharmacology vol 73 no 1-2 pp 233ndash2412000
[34] P W Doetsch J M Cassady and J L McLaughlin ldquoCac-tus alkaloids XL Identification of mescaline and other 120573-phenethylamines in Pereskia Pereskiopsis and Islaya by use offluorescamine conjugatesrdquo Journal of Chromatography A vol189 no 1 pp 79ndash85 1980
[35] I R A Wahab C C Guilhon P D Fernandes and F BoylanldquoAnti-nociceptive activity of Pereskia bleo Kunth (Cactaceae)leaves extractsrdquo Journal of Ethnopharmacology vol 144 no 3pp 741ndash746 2012
[36] S N AMalek N AWahabH Yaacob et al ldquoCytotoxic activityof Pereskia bleo (Cactaceae) against selected human cell linesrdquoInternational Journal of Cancer Research vol 4 no 1 pp 20ndash272008
Evidence-Based Complementary and Alternative Medicine 11
[37] B Hassanbaglou A A Hamid A Roheeyati et al ldquoAntioxidantactivity of different extracts from leaves of Pereskia bleo (Cac-taceae)rdquo Journal of Meidinal Plants Research vol 6 no 15 pp2932ndash2937 2012
[38] S I Abbdewahab N M Ain A B Abdul M M E Tahaand T A T Ibrahim ldquoEnergy-dispersive X-raymicroanalysis ofelementsrsquo content and antimicrobial properties of Pereskia bleoandGoniothalamus umbrosusrdquoAfrican Journal of Biotechnologyvol 8 no 10 pp 2375ndash2378 2009
[39] S Y Liew E J Stanbridge K Yusoff and N ShafeeldquoHypoxia affects cellular responses to plant extractsrdquo Journal ofEthnopharmacology vol 144 no 2 pp 453ndash456 2012
[40] M L Tan S F Sulaiman N Najimuddin M R Samian and TS T Muhammad ldquoMethanolic extract of Pereskia bleo (Kunth)DC (Cactaceae) induces apoptosis in breast carcinoma T47-D cell linerdquo Journal of Ethnopharmacology vol 96 no 1-2 pp287ndash294 2005
[41] K Philip S N A Malek W Sani et al ldquoAntimicrobial activityof some medicinal plants from Malaysiardquo American Journal ofApplied Sciences vol 6 no 8 pp 1613ndash1617 2009
[42] T Ruegg A I Calderon E F Queiroz et al ldquo3-farnesyl-2-hydroxybenzoic acid is a new anti-Helicobacter pylori com-pound from Piper multiplinerviumrdquo Journal of Ethnopharma-cology vol 103 no 3 pp 461ndash467 2006
[43] L Rahalison M Hamburger K Hostettmann et al ldquoScreeningfor antifungal activity of Panamanian plantsrdquo InternationalJournal of Pharmacognosy vol 31 no 1 pp 68ndash76 1993
[44] A P D Candolle ldquoPereskia bleo (Kunth) DCrdquo 2011 httpwwwtropicosorgName5100482
[47] M Gardener ldquoTropical plants library onlinerdquo 2014 httpmgonlinecomarticlesexoticsaspx
[48] S Kurt ldquoStem of P grandifoliardquo 2014 httpwwwbiolibde[49] NRCS ldquoNatural Resources and Conservation Service of
USDA Plant profile of P grandifolia Hawrdquo 2013 httpplantsusdagovcoreprofilesymbol=PEGR14
[50] D C Sanders A S Grayson andT JMonaco ldquoMineral contentof tomato (Lycopersicon esculentum) and four competing weedspeciesrdquoWeed Science vol 29 no 5 pp 590ndash593 1981
[51] J M Geleijnse J C Witteman A A Bak J H den Breeijenand D E Grobbee ldquoReduction in blood pressure with a lowsodium high potassium high magnesium salt in older subjectswith mild to moderate hypertensionrdquo British Medical Journalvol 309 no 6952 pp 436ndash440 1994
[52] A Marston G Dudan M P Gupta P N Solis M D Correaand K Hostettmann ldquoScreening of Panamanian plants formolluscicidal activityrdquo Pharmaceutical Biology vol 34 no 1 pp15ndash18 1996
[53] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999
[54] T Komiya M Kyohkon S Ohwaki et al ldquoPhytol inducesprogrammed cell death in human lymphoid leukemia Molt 4Bcellsrdquo International Journal of Molecular Medicine vol 4 no 4pp 377ndash380 1999
[55] M Gerber M C Boutron-Ruault S Hercberg E Riboli AScalbert and M H Siess ldquoFood and cancer state of the art
about the protective effect of fruits and vegetablesrdquo Bulletin duCancer vol 89 no 3 pp 293ndash312 2002
[56] V di Matteo and E Esposito ldquoBiochemical and therapeuticeffects of antioxidants in the treatment of Alzheimerrsquos diseaseParkinsonrsquos disease and amyotrophic lateral sclerosisrdquo CurrentDrug Targets-CNSampNeurological Disorders vol 2 no 2 pp 95ndash107 2003
[57] P Knekt R Jarvinen A Reunanen and J Maatela ldquoFlavonoidintake and coronary mortality in Finland a cohort studyrdquoBritish Medical Journal vol 312 no 7029 pp 478ndash481 1996
[58] R A Mustafa A Abdul Hamid S Mohamed and F A BakarldquoTotal phenolic compounds flavonoids and radical scavengingactivity of 21 selected tropical plantsrdquo Journal of Food Sciencevol 75 no 1 pp C28ndashC35 2010
[59] E B Breidenstein C de la Fuente-Nunez and R E HancockldquoPseudomonas aeruginosa all roads lead to resistancerdquo Trendsin Microbiology vol 19 no 8 pp 419ndash426 2011
[60] C Chu C-H ChiuW-YWu C-H Chu T-P Liu and J T OuldquoLarge drug resistance virulence plasmids of clinical isolates ofSalmonella enterica serovar Choleraesuisrdquo Antimicrobial Agentsand Chemotherapy vol 45 no 8 pp 2299ndash2303 2001
[61] K Hiramatsu H Hanaki T Ino K Yabuta T Oguri andF Tenover ldquoMethicillin-resistant Staphylococcus aureus clini-cal strain with reduced vancomycin susceptibilityrdquo Journal ofAntimicrobial Chemotherapy vol 40 no 1 pp 135ndash136 1997
[62] I TMatsuse Y A LimMHattori M Correa andM P GuptaldquoA search for anti-viral properties in Panamanian medicinalplants the effects on HIV and its essential enzymesrdquo Journal ofEthnopharmacology vol 64 no 1 pp 15ndash22 1998
[63] M Hattori T Nakabayashi Y A Lim et al ldquoInhibitory effectsof various Ayurvedic and Panamanian medicinal plants onthe infection of herpes simplex virus-1 in vitro and in vivordquoPhytotherapy Research vol 9 no 4 pp 270ndash276 1995
[64] I Kola and J Landis ldquoCan the pharmaceutical industry reduceattrition ratesrdquoNature Reviews Drug Discovery vol 3 no 8 pp711ndash716 2004
[65] H Olson G Betton D Robinson et al ldquoConcordance ofthe toxicity of pharmaceuticals in humans and in animalsrdquoRegulatory Toxicology and Pharmacology vol 32 no 1 pp 56ndash67 2000
Common namesButarrar (Kuna Indian) [22]Cak Sing Cam Qi xing zhen (Chinese) [1 8 23]Chupa Chupa melon Najiı Najii De Culebra Naju de esoubas and Bleo de chupa (Spanish) [2 21 24]Perescia [7]Pokok Jarum Tujuh Bilah (Malay) [2 25]Rose cactus Bleo Chinese rose Spinach cactus wax rose and orange rose cactus (English) [1 6 7 21 24 26]
Table 3 Traditional usage and methods of preparation of P bleo
Purpose Method of preparation References
Detoxification and prevention of cancer Making tea by boiling the leaves andor the fruit and then drinking itwarm or cool [27ndash30]
Dietary purposes and health maintenance Eating the raw leaf flower and fruit [19 28]Health maintenance and revitalizing thebody
Making juice from the leaves and boiling in water and drinking everymorning [30]
To alleviate muscleache Making decoction from the leaves and then using as a warm bath formuscle ache [29]
To alleviate stomachache
Preparing ldquoina kuamakaletrdquo the inflorescence is mixed with theexcrements of red ants by using a special mortar and then moistenedwith water The resulted mass is moulded to oval shape objects whichare dried in sun When using the remedy these balls are rubbed in asmall container with a small amount of water
[29]
To treat hemorrhoid hypertensiondiabetes infections headache andinflammatory conditions (rheumatismand asthma)
No information is available in the literature [28 31 32]
To neutralize the effects of the snakebites No information is available in the literature [33]
P grandifolia has thicker uncorrugated leaves pink topurplish-pink flowers and longer but fewer spines on thestems [11] Figure 1 shows the photographs of different partsof P bleo and P grandifolia Although they are differentspecies anatomical similarities in these two species supportthe evolution theory for cactus family [18]
32 Traditional Usage P bleo has been used for various pur-poses In some areas it is used as a food spice [1 7] Thisplant has been eaten raw as vegetables by some people inMalaysia and China or taken as a concoction brewed fromfresh leaves [19 36] In addition it is taken for detoxificationand revitalizing the body [27 28 40] Its fruit is consumedby some ethnic groups in Panama as a wild fruit [26] Theleaves of P bleo have been traditionally used to treat can-cer hemorrhoid hypertension diabetes [32 40] infectionsgastric pain headache ulcer and inflammatory conditions
like rheumatism and asthma [28 31] Indigenous Colombianshave used P bleo to neutralize the effects of snakebites [33]to relax spastic muscles and to alleviate muscle aches [29]Apart from dietary andmedicinal uses this plant is a suitablebarrier hedge because of its sharp spines strong stem andinsect repellant properties [21] In Central America KunaIndians used the crushed leaves to clarify drinking water[12] Different methods of preparation have been reportedfor the plant It is usually taken raw or as a decoction of itsfresh leaves Table 3 shows the traditional usage and differentpreparation methods of P bleo To the best of our knowledgeinformation on the specific preparation methods for some ofthe indicated traditional usages is not available
33 Phytochemistry The leaves are the most commonly usedpart of P bleo in traditional medicine Hence they have beenmore studied compared to the other plant parts So far 20
4 Evidence-Based Complementary and Alternative Medicine
Table 4 Reported phytoconstituents in the leaves and fruits of P bleo
Plant part Class of the constituents Constituents Reference
Fruit Carotenoids Lutein (120573e-carotene-331015840-diol) [26 37]Zeaxanthin (120573120573-carotene-331015840-diol)
Table 5 Percentage ( ww) of mineral contents in the leaves of Pbleo [38]
Mineral elements Percentage weight ()Carbon 506Oxygen 354Magnesium 04Phosphorus 04Sulfur 15Chlorine 12Potassium 102Aluminium NDlowast
Calcium 03Silicon NDFerrum (Iron) NDlowastND not detected
phytoconstituents have been reported in the leaves and twocomponents from the fruit as shown in Table 4 These com-ponents include alkaloids fatty acids glycosides lactonesphenolic sterol terpenoid and carotenoid compounds Themajor isolated component from P bleo leaves is phytol [27]In addition Doetsch et al [34] reported the isolation ofthree alkaloids namely 34-dimethoxy-120573-phenethylamine(mescaline) 3-methoxytyramine and tyramine from theleaves of this plant Vitamin E (120572-tocopherol) [36 37] which
is well known for its antioxidant properties 24-ditert-butylphenol and dihydroactinidiolide were isolated throughbioassay-guided fractionation by Malek et al [36] Murillo etal [26] analyzed the fruit of P bleo for lutein and zeaxanthincontents The total carotenoid content of the fruit was foundto be 133 120583gg making P bleo fruit a high carotenoid foodsource among the wild fruits in Panama
Themineral content of the leaves was also investigated byusing energy-dispersive X-ray microanalysis Table 5 showsthe weight percentage of the minerals reported by Abbde-wahab et al [38] As can be seen P bleo leaves are richin potassium (1016) This is more than two times of thepotassium content of tomato (45) a vegetable known tobe high in potassium [50] It has been shown that a highpotassium diet has an important role in lowering bloodpressure [51] Therefore it might be one of the possiblereasons for the traditional usage of P bleo as a treatment forhypertension [31]
34 Pharmacological Properties Pharmacological evaluationof plants is based on their traditional uses Cancer is oneof the main causes of mortality and morbidity Since Pbleo is traditionally used to prevent and treat cancer [2830 40] it has been most studied for its antiproliferativeand cancer protective properties [8 22 28 32 36 39 40]This is followed by investigations of its antimicrobial andantiparasitic effects in vitro [8 38 41ndash43 52] The snake
Evidence-Based Complementary and Alternative Medicine 5
(a) (b)
(c) (d)
(e) (f)
Figure 1 Photographs of different plant parts of P bleo and P grandifolia (a) Flower of P bleo (b) lower of P grandifolia [47] (c) stem andspines of P bleo (d) stem and spines of P grandifolia [48] (e) ripe fruits and seeds of P bleo and (f) ripe fruits and seeds of P grandifolia [49]
venom neutralizing properties [33] antinociceptive effects[35] and toxicity [22 31] of this plant have been evaluatedthrough in vivo studies
341 Antiproliferative Properties The effects of different Pbleo extracts have been reported on various cell lines in vitroThe crude methanol extract and its ethyl acetate fraction had
significant cytotoxic effects against human nasopharyngealepidermoid carcinoma cell line (KB) [36] In addition theethyl acetate fraction was more active than the methanolextract against human colon carcinoma (HCT116) and hor-mone dependent breast carcinoma cell lines (MCF7) [36]Table 6 shows the reported IC
50values (120583gmL) for the
antiproliferative effects of P bleo extracts and fractions
6 Evidence-Based Complementary and Alternative Medicine
Table6IC
50values
(120583gmL)
ofPbleo
leafextractsandfractio
nson
different
celllin
es
Cellline
Extractsandfractio
ns(IC 5
0120583gmL)
Positivec
ontro
l(IC
50120583
gmL)
Negativec
ontro
lRe
ferences
Methano
lWater
Hexane
Dichlorom
ethane
Ethylacetate
4T1
gt50
gt50
NA
NA
NA
Cisplatin
(NA)
NA
[32]
CasK
i40
5mdash
895
NA
58Doxorub
icin
(6times10minus3)
NA
[36]
CEM-ss
mdashNA
mdashmdash
mdashNA
VC[8]
HT2
9andHCT
116gt30
NA
gt30
gt30
gt30
NA
VC[8]
416
mdash675
NA
22Doxorub
icin
(36times10minus1)
NA
[36]
KB65
mdash28
NA
45
Doxorub
icin
(12times10minus2)
NA
[36]
MCF
-7gt30
NA
gt30
gt30
gt30
NA
VC[8]
39mdash
25NA
28Doxorub
icin
(75times10minus2)
NA
[36]
MRC
-5mdash
mdashmdash
NA
mdashDoxorub
icin
(55times10minus1)
NA
[36]
NIH
3T3
ge200
ge200
NA
NA
NA
Cisplatin
NA
[32]
Saos-2
mdashNA
NA
NA
NA
Cisplatin
NA
[39]
T-47D
2NA
NA
NA
NA
DNaseI
VC[40]
V79
mdashNA
NA
NA
NA
Nitracrin
eVC
[22]
IC5050
ofmaxim
umcellinhibitio
nIC
50lt20120583gmLisconsidered
activ
e100gtIC
50gt20120583gmLisrelativ
elyactiv
eandIC
50gt100isno
tactive[8]
(mdash)no
activ
ity
4T1mou
semam
marycancer
celllin
eCa
sKihu
man
cervicalcarcinom
acelllin
eCE
M-sshu
man
T-4lymph
oblasto
idcelllin
eHT2
9andHCT
116hum
ancoloncarcinom
acelllin
eKB
hum
annasoph
aryn
geal
epidermoidcarcinom
acelllin
eMCF
-7h
ormon
edependent
breastcarcinom
acelllin
eMRC
-5n
ormalhu
man
fibroblastcelllinesN
IH3T3
normalmou
sefib
roblastcelllineSaos-2hum
anosteosarcomacell
lineT-47Dhum
anbreastcarcinom
acelllineV79C
hinese
hamste
rlun
gfib
roblasts
NAnot
available
VCvehiclecontrol
Evidence-Based Complementary and Alternative Medicine 7
Table 7 Reported IC50 values (120583gmL) of selected P bleo phytoconstituents on human cell lines [28]
Compound IC50 (120583gmL) of different cell linesKB MCF7 CasKi HCT 116 A549 MRC-5
Dihydroactinidiolide 67 30 40 5 97 913120573-sitosterol gt100 72 62 gt100 78 gt10024-ditertbutylphenol 081 575 45 29 6 20120572-tocopherol 8 75 6 31 6 305Phytol 71 34 18 100 31 741Mixture of sterols gt100 gt100 gt100 gt100 gt100 gt100Doxorubicin 13 times 10minus2 76 times 10minus2 60 times 10minus3 36 times 10minus1 22 times 10minus1 55 times 10minus1
A549 human lung carcinoma cell line CasKi human cervical carcinoma cell Line HCT116 human colon carcinoma cell Line KB human nasopharyngealepidermoid carcinoma cell Line MCF-7 hormone dependent breast carcinoma cell Line MRC-5 normal human fibroblast cell Lines
Gupta et al [22] reported high tumor inhibition activityin ldquopotato disc inhibition assayrdquo using crown gall tumors(LC5077 ppm)Their result was accompanied by a significant
DNA peak reduction in the DNA intercalation test for themethanol extract of the whole plant
To date no report is available on the in vivo antiprolifer-ative activities of P bleo
(1) Cytotoxic Components Some of the cytotoxic componentsin P bleo have been reported Table 7 shows the reported IC
50
(120583gmL) values of these components in the different humancell lines The effects of these compounds and the mixture ofthe isolated sterols were not as high as doxorubicin that isa chemotherapy drug [28] In another study phytol isolatedfrom P bleo leaves was found to have a significant antitumoractivity against some mouse cancer cell lines [36]
(2) Proposed Antiproliferative Mechanism The antiprolifera-tive activity of the methanol extract of P bleo against humanbreast carcinoma cell line (T-47D) was found to be apoptoticin nature through the activation of caspase-3 and c-mycpathways [40] Caspase-3 and c-myc are frequently activateddeath proteases which catalyze the specific cleavage of manykey cellular proteins They are also essential for normaldevelopment of the tissues as well as apoptosis in the tissuesand cell types [53] Komiya et al [54] reported the inductionof apoptosis as a mechanism of action for cytotoxic activityof phytol DNA intercalation is another proposedmechanismof antiproliferative activity for P bleo [22] However in somestudies P bleo did not show appreciable cytotoxic effect [32]Differences in the sources of plants extractionmethods assaymethods and cell lines can be the possible reasons for thesediscrepancies On the other hand P bleo may contain someprodrugs which are metabolized to the active metabolitesTherefore further studies are needed to better understand itsantiproliferative activity
Apart from the cytotoxic activities against cancer celllines crudemethanol extract and its fractions (hexane waterand ethyl acetate) did not show any cytotoxicity to the normalhuman fibroblast cell lines MRC-5 [36]
342 Antioxidant Activity The adverse effects of oxida-tive stress on human health have become a serious issueOxidative stress causes production of free radicals in thebody that facilitate the development of degenerative diseasessuch as cardiovascular diseases cancers neurodegenerativedisorders [55] Alzheimerrsquos and inflammatory diseases [56]One solution to this problem is to supplement the diet withantioxidant compounds found in natural plant sources [57]Hence in the literature the antioxidant effects of P bleo wereevaluated using different assays as follows
22-Diphenyl-1-picrylhydrazyl Hydrate (DPPH) Assay Themethanol dichloromethane ethyl acetate and hexaneextracts of P bleo leaves were tested [8 25] The hexaneextract exhibited the most effective radical scavengingactivity (EC
50210 120583gmL) followed by the ethyl acetate
extract (EC50
225120583gmL) This spectrophotometric assayuses a stable radical 221015840-diphenylpicrylhydrazyl (DPPH) asa reagent [8 25]
Ferric Reducing Antioxidant Potential Assay (FRAP) Thehexane water and methanol extracts of P bleo leaves werefound to reduce Fe3+ferric cyanide complex to the ferrousform Although the reduction was statistically significant itwas not more than ascorbic acid (vitamin C) and butylatedhydroxyanisole (BHA) as positive controls [25] Hassanba-glou et al [37] compared the antioxidant activity of the ethylacetate extract with that of hexane ethanol and methanolextracts They showed that the ethyl acetate extract hadsignificantly higher antioxidant properties compared to therest of the tested extracts FRAP measures the ability of testsamples to reduce ferric ion to the ferrous form of TPTZ(246-tripyridyl-s-triazine)
120573-Carotene-Linoleic Bleaching AssayThe ethyl acetate extractof P bleo demonstrated the strongest antioxidant activityfollowed by the methanol extract reported by Sim et al [25]In this assay the linoleate free radicals formed during thereaction are neutralized by antioxidants
8 Evidence-Based Complementary and Alternative Medicine
Table8Re
ported
effectsof
Pbleo
extractson
theg
rowth
ofselected
bacteriaandfung
i
Organism
Antibacteria
land
antifun
galeffectof
thee
xtracts
Positivec
ontro
lRe
ferences
Methano
lWater
Hexane
Dichloroethane
Ethylacetate
Chloroform
Bacillussubtilisa
minusNA
minusminus
minusNA
Streptom
ycinlowast
[8]
minusminus
minusNA
minusNA
Gentamicinampicillin
[41]
NA
NA
minusminus
NA
NA
Streptom
ycin
[38]
Escherich
iacolib
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Escherich
iacolia
minusminus
minusNA
minusNA
Gentamicinampicillin
[41]
Helicobacterpylorib
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Klebsiella
pneumoniaeb
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Methicillin
resistant
Staphylococcus
aureus
aminus
NA
minus++
+minus
NA
Streptom
ycinlowast
[8]
NA
NA
minus++
NA
NA
Streptom
ycin
[38]
Mycobacteriu
msm
egmatisb
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Pseudomonas
aeruginosa
a++
NA
+++
++
NA
Streptom
ycin
[8]
+minus
minusNA
+NA
Gentamicinampicillin
[41]
NA
NA
+++
+NA
NA
Streptom
ycinlowast
[38]
Pseudomonas
aeruginosa
bminus
NA
NA
minusNA
NA
Streptom
ycin
[42]
Salm
onellacholeraesuisa
++NA
+++
minusminus
NA
Streptom
ycinlowast
[8]
NA
NA
+++
minusNA
NA
Streptom
ycin
[38]
Staphylococcus
aureus
bminus
NA
NA
minusNA
NA
Streptom
ycin
[42]
Staphylococcus
aureus
aminus
minusminus
NA
minusNA
Gentamicinampicillin
[41]
Cand
idaalbicans
cminus
minusNA
NA
NA
minusProp
icon
azolemicon
azole
[43]
Cand
idaalbicans
bminus
NA
NA
minusNA
NA
Amph
otericin
B[42]
Cladosporiu
mcucumerinum
c+
+NA
NA
NA
+Prop
icon
azolemicon
azole
[43]
a Thes
creening
fora
ntibacteria
leffectwas
carriedou
tbyd
eterminingthez
oneo
finh
ibition
usingpaperd
isc+
stand
sfor
activ
itybetween6ndash
9mm+
+sta
ndsfor
activ
itybetween9ndash
14mm+
++stands
fora
ctivity
morethan14mm
[38]
b (+)
stand
sfor
activ
ityat100120583
gmLforE
coliS
aureusK
pneum
oniaeMsmegmatis
CalbicanceP
aeruginosa
andat125120583gmLforH
pylori(minus)stand
sfor
inactiv
esam
ples
c agaro
verla
yassayand(+)stand
sfor
activ
eextractsa
t50120583
gmL(minus)stand
sfor
inactiv
eextract
NAnot
applicableas
thereisn
orepo
rtin
theliterature
lowastStreptom
ycin
show
ed20
to23
mm
inhibitio
nzoneTh
eresto
fthe
studies
didno
treportthe
exactvalue
oftheinh
ibition
fortheirpo
sitivec
ontro
ls
Evidence-Based Complementary and Alternative Medicine 9
In general although different studies used plant materialsfrom different sources and nonsimilar extraction methodsethyl acetate and hexane extracts appear to be the strongestantioxidant extracts from the P bleo leaves [8 25 37]Moreover this antioxidant capacity is strongly associatedwith the total phenolic compounds and flavonoid content ofthe plant leaves [25 37 58] The above studies suggest thatP bleo has antioxidant properties which can be one of thepossible reasons for its traditional usage for detoxificationand prevention of cancer
343 Antimicrobial Properties P bleo has been shown topossess antibacterial antiviral and antifungal properties invitro Table 8 shows the effect of P bleo extracts on selectedbacteria and fungi As can be seen the methanol andhexane extracts demonstrated great antibacterial activitiesagainst Salmonella choleraesuis and Pseudomonas aeruginosaIn addition its dichloromethane extract showed promisingantibacterial effect againstMethicillin resistant Staphylococcusaureus [8 38] All of the mentioned bacteria are amongthe main causes of nosocomial infections and they havebeen developing antibiotic resistance [59ndash61] Therefore thepotential antibacterial activity of P bleo needs to be furtherinvestigated to identify the lead(s) antibacterial compo-nent(s)
The antifungal activity of the water and methanol extractof P bleo leaves against Cladosporium cucumerinum a plantpathogenic fungus has been reported [43] but they were notactive against Candida albicans a common human pathogen[42 43]
The antiviral properties of the water and methanolextracts of P bleo leaves were evaluated against HerpesSimplex Virus-I (HSV-1) andHuman Immunodeficiency Virus(HIV) by Matsuse et al [62] Both of the extracts demon-strated anti-HIV activity However the result of this studywas not promising because of the low selectivity index of094 Besides in another study by Hattori et al [63] the sameextracts did not demonstrate any antiviral activity againstHSV-1 In general the available data on the antiviral activityof P bleo is neither sufficient nor conclusive Thereforefurther research needs to be carried out
344 Antiparasitic Properties The only antiparasitic inves-tigation on P bleo was reported by Marston et al [52] Intheir study the chloroform methanol and water extractsof this plant did not exert any antiparasitic activity againstschistosomiasis
345 Neutralizing Snake Venom Otero et al [33] evaluatedthe neutralizing effect of the ethanol extract of P bleo onhemorrhagic activity of ldquoBothrops atrox venomrdquo in miceThisextract did not show any neutralizing effect against the testedvenom
346 Antinociceptive Properties Wahab et al [35] evaluatedthe antinociceptive activity of the ethanol extract and itsfractions using two in vivo analgesic models peripheralformalin-induced licking and acetic acid-induced abdominal
writhing They showed that the ethanol extract hexanefraction dichloromethane fraction and ethyl acetate fractionof P bleo had moderate antinociceptive effects However nocompound was identified in their study
35 Toxicity Studies Acute toxicity effect of the leaversquosextracts of P bleo was evaluated by in vitro and in vivostudies Er et al [32] showed that the water extract may formmutagenic compound(s) upon metabolization by the liverenzymes in vitro In another study by Gupta et al [22] themethanol extract of the whole plant had moderate toxicity inbrine shrimp toxicity assay (LD
5077 ppm) In the only in vivo
study by Sim et al [31] the methanol extract did not have anytoxicity effect on ICR mice (LD
50gt 2500mgkg) Although
animalmodels have around 70ndash80 predictability for humantoxicities [64 65] the long term toxicity and themutagenicityof metabolites of P bleo should be further investigated
4 Conclusion
A comprehensive review on Pereskia bleo has been presentedIt provides an overview of the botanical characteristics tra-ditional usage phytoconstituents pharmacological activitiesand safety of P bleo The current review highlights theassociation between the traditional usage of the plant andthe reported anticancer antibacterial and antinociceptiveeffects tested in different studies Although P bleo has beentraditionally used for a variety of therapeutic and prophy-lactic purposes only a few of them has been investigatedHence more research is warranted to further study itsbiological activities and chemical properties to understandits traditional usage and to develop novel therapeuticsUnderstanding the traditional uses knowing the availablescientific evidences and identifying the gaps in research willallow the proper translation of promising research results intoa safe and efficacious usage of herbal medicine and discoveryof new therapeutics It will also assist in setting appropriatepolicy and guidelines in the usage of herbal medicine
Conflict of Interests
All authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgments
Funding from the National University of Singapore (NUS)research Grant (R-148-000-137-112 to KHL) and LeewardPacific Pte Ltd (R-148-000-140-592 to KHL) and researchscholarship from the Singapore International GraduateAward (SINGA SZ) are acknowledged
References
[1] C Wiart Medicinal Plants of Asia and the Pacific Drugs of theFuture World Scientific Singapore 2006
[2] N L Britton and J N Rose The Cactaceae Descriptions andIllustrations of Plants of the Cactus Family Dover PublicationsWashington DC USA 2009
10 Evidence-Based Complementary and Alternative Medicine
[3] E J Edwards and M J Donoghue ldquoPereskia and the origin ofthe cactus life-formrdquo American Naturalist vol 167 no 6 pp777ndash793 2006
[4] E J Edwards R Nyffeler and M J Donoghue ldquoBasal cactusphylogeny implications of Pereskia (Cactaceae) paraphyly forthe transition to the cactus life formrdquo American Journal ofBotany vol 92 no 7 pp 1177ndash1188 2005
[5] R M Ogburn and E J Edwards ldquoAnatomical variation in Cac-taceae and relatives trait lability and evolutionary innovationrdquoAmerican Journal of Botany vol 96 no 2 pp 391ndash408 2009
[6] CM Boo C LOu-Yang andKOmar-Hor 1001Garden Plantsin Singapore National Parks Board Singapore 2nd edition2007
[7] Singapore Npark Board NParks FloraampFouna web 2010httpsflorafaunawebnparksgovsgSpecial-Pagesplant-detailaspxid=2324
[8] S I A Wahab A B Abdul S M Mohan A S Al-Zubairi MM Elhassan andMY Ibrahim ldquoBiological activities ofPereskiableo extractsrdquo International Journal of Pharmacology vol 5 no1 pp 71ndash75 2009
[9] R T Barcenas C Yesson and J A Hawkins ldquoMolecular sys-tematics of the CactaceaerdquoCladistics vol 27 no 5 pp 470ndash4892011
[10] K Y Chong H T Tan and R T Corlett A Checklist of theTotal Vascular Plant Flora of Singapore Native Naturalised andCultivated Species Raffles Museum of Biodiversity ResearchNational University of Singapore Singapore 2009 httprmbrnusedusgraffles museum pubflora of singapore tcpdf
[11] A M Sri Nurestri K S Sim and A W Norhanom ldquoPhy-tochemical and cytotoxic investigations of Pereskia grandifoliaHaw (Cactaceae) leavesrdquo Journal of Biological Sciences vol 9no 5 pp 488ndash493 2009
[12] E Anderson The Cactus Family pp 566ndash568 Timber PressPuritana Ore USA 1st edition 2001
[13] R P Wunderlin and B F Hansen ldquoAtlas of Florida VascularPlantsrdquo 2008 httpwwwplantatlasusfedu
[14] N P Taylor D Zappi P Braun and M Machado ldquoPereskiaaculeata Iucn Red List of Threatened Species Version 2013 2rdquo2013 httpwwwiucnredlistorg
[15] E Pooley A Field Guide to Wild Flowers KwaZulu Natal and theEastern Region Natal Flora Publications Trust Durban SouthAfrica 1999
[16] A G I Natural Heritage Trust ldquoWeedManagementGuide Leafcactus Pereskia aculeatardquo 2003 httpwwwenvironmentgovaubiodiversityinvasiveweedspublicationsguidelinesalertpubsp-aculeatapdf
[18] B E Leuenberger ldquoPereskia Maihuenia and Blossfeldia-taxonomic history updates and notesrdquo Haseltonia no 14 pp54ndash93 2008
[19] J Nugent ldquoPermaculture Plants agaves and cactirdquo 2007 httpbooksgooglecomsgbooksid=YVwMM2OdO34Campq=Pereskia+bleov=snippetampq=Pereskia20bleoampf=false
[20] B E Leuenberger ldquoHumboldt amp Bonplandrsquos Cactaceae in theherbaria at Paris and Berlinrdquo Willdenowia vol 32 pp 137ndash1532002
[21] KA LiamasTropical Flowering Plants AGuide to Identificationand Cultivation Timber Press Portland Ore USA 2003
[22] M P Gupta A Monge G A Karikas et al ldquoScreening of Pana-manian medicinal plants for brine shrimp toxicity crown
gall tumor inhibition cytotoxicity and DNA intercalationrdquoPharmaceutical Biology vol 34 no 1 pp 19ndash27 1996
[23] C C Kazama D T Uchida K N Canzi et al ldquoInvolvementof arginine-vasopressin in the diuretic and hypotensive effectsof Pereskia grandifoliaHaw (Cactaceae)rdquo Journal of Ethnophar-macology vol 144 no 1 pp 86ndash93 2012
[25] K S Sim A M Sri Nurestri and A W Norhanom ldquoPhenoliccontent and antioxidant activity of crude and fractionatedextracts of Pereskia bleo (Kunth) DC (Cactaceae)rdquo AfricanJournal of Pharmacy and Pharmacology vol 4 no 5 pp 193ndash201 2010
[26] EMurillo A JMelendez-Martınez and F Portugal ldquoScreeningof vegetables and fruits from Panama for rich sources of luteinand zeaxanthinrdquo Food Chemistry vol 122 no 1 pp 167ndash1722010
[27] K Hostettmann A Marston M Maillard and M HamburgerPhytochemistry of Plants Used in Traditional Medicine pp 373ndash376 Oxford University Press Oxford UK 1995
[28] S N A Malek S K Shin N A Wahab and H Yaacob ldquoCyto-toxic components of Pereskia bleo (Kunth) DC (Cactaceae)leavesrdquoMolecules vol 14 no 5 pp 1713ndash1724 2009
[29] M P Gupta A Correa DMireya et al ldquoMedicinal plant inven-tory of Kuna Indians part 1rdquo Journal of Ethnopharmacology vol40 no 2 pp 77ndash109 1993
[30] A Rahmat F P Saib and N A Buslima ldquoComparing theeffect of ficus benjamina extract and Pereskia saecnarosa extracton tthe level of micro and macro minerals in normal andinduced liver cancer ratsrdquo in Proceedings of the 4th InternationalConference on Biomedical Engineering in Vietnam pp 208ndash2121980
[31] K S Sim A M Sri Nurestri S K Sinniah K H Kim and AW Norhanom ldquoAcute oral toxicity of Pereskia bleo and Pereskiagrandifolia inmicerdquo PharmacognosyMagazine vol 6 no 21 pp67ndash70 2010
[32] H M Er E Cheng and A K Radhakrishnan ldquoAnti-proliferative and mutagenic activities of aqueous and methanolextracts of leaves from Pereskia bleo (Kunth) DC (Cactaceae)rdquoJournal of Ethnopharmacology vol 113 no 3 pp 448ndash456 2007
[33] R Otero V Nunez J Barona et al ldquoSnakebites and ethnob-otany in the northwest region of Colombia part III neutral-ization of the haemorrhagic effect of Bothrops atrox venomrdquoJournal of Ethnopharmacology vol 73 no 1-2 pp 233ndash2412000
[34] P W Doetsch J M Cassady and J L McLaughlin ldquoCac-tus alkaloids XL Identification of mescaline and other 120573-phenethylamines in Pereskia Pereskiopsis and Islaya by use offluorescamine conjugatesrdquo Journal of Chromatography A vol189 no 1 pp 79ndash85 1980
[35] I R A Wahab C C Guilhon P D Fernandes and F BoylanldquoAnti-nociceptive activity of Pereskia bleo Kunth (Cactaceae)leaves extractsrdquo Journal of Ethnopharmacology vol 144 no 3pp 741ndash746 2012
[36] S N AMalek N AWahabH Yaacob et al ldquoCytotoxic activityof Pereskia bleo (Cactaceae) against selected human cell linesrdquoInternational Journal of Cancer Research vol 4 no 1 pp 20ndash272008
Evidence-Based Complementary and Alternative Medicine 11
[37] B Hassanbaglou A A Hamid A Roheeyati et al ldquoAntioxidantactivity of different extracts from leaves of Pereskia bleo (Cac-taceae)rdquo Journal of Meidinal Plants Research vol 6 no 15 pp2932ndash2937 2012
[38] S I Abbdewahab N M Ain A B Abdul M M E Tahaand T A T Ibrahim ldquoEnergy-dispersive X-raymicroanalysis ofelementsrsquo content and antimicrobial properties of Pereskia bleoandGoniothalamus umbrosusrdquoAfrican Journal of Biotechnologyvol 8 no 10 pp 2375ndash2378 2009
[39] S Y Liew E J Stanbridge K Yusoff and N ShafeeldquoHypoxia affects cellular responses to plant extractsrdquo Journal ofEthnopharmacology vol 144 no 2 pp 453ndash456 2012
[40] M L Tan S F Sulaiman N Najimuddin M R Samian and TS T Muhammad ldquoMethanolic extract of Pereskia bleo (Kunth)DC (Cactaceae) induces apoptosis in breast carcinoma T47-D cell linerdquo Journal of Ethnopharmacology vol 96 no 1-2 pp287ndash294 2005
[41] K Philip S N A Malek W Sani et al ldquoAntimicrobial activityof some medicinal plants from Malaysiardquo American Journal ofApplied Sciences vol 6 no 8 pp 1613ndash1617 2009
[42] T Ruegg A I Calderon E F Queiroz et al ldquo3-farnesyl-2-hydroxybenzoic acid is a new anti-Helicobacter pylori com-pound from Piper multiplinerviumrdquo Journal of Ethnopharma-cology vol 103 no 3 pp 461ndash467 2006
[43] L Rahalison M Hamburger K Hostettmann et al ldquoScreeningfor antifungal activity of Panamanian plantsrdquo InternationalJournal of Pharmacognosy vol 31 no 1 pp 68ndash76 1993
[44] A P D Candolle ldquoPereskia bleo (Kunth) DCrdquo 2011 httpwwwtropicosorgName5100482
[47] M Gardener ldquoTropical plants library onlinerdquo 2014 httpmgonlinecomarticlesexoticsaspx
[48] S Kurt ldquoStem of P grandifoliardquo 2014 httpwwwbiolibde[49] NRCS ldquoNatural Resources and Conservation Service of
USDA Plant profile of P grandifolia Hawrdquo 2013 httpplantsusdagovcoreprofilesymbol=PEGR14
[50] D C Sanders A S Grayson andT JMonaco ldquoMineral contentof tomato (Lycopersicon esculentum) and four competing weedspeciesrdquoWeed Science vol 29 no 5 pp 590ndash593 1981
[51] J M Geleijnse J C Witteman A A Bak J H den Breeijenand D E Grobbee ldquoReduction in blood pressure with a lowsodium high potassium high magnesium salt in older subjectswith mild to moderate hypertensionrdquo British Medical Journalvol 309 no 6952 pp 436ndash440 1994
[52] A Marston G Dudan M P Gupta P N Solis M D Correaand K Hostettmann ldquoScreening of Panamanian plants formolluscicidal activityrdquo Pharmaceutical Biology vol 34 no 1 pp15ndash18 1996
[53] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999
[54] T Komiya M Kyohkon S Ohwaki et al ldquoPhytol inducesprogrammed cell death in human lymphoid leukemia Molt 4Bcellsrdquo International Journal of Molecular Medicine vol 4 no 4pp 377ndash380 1999
[55] M Gerber M C Boutron-Ruault S Hercberg E Riboli AScalbert and M H Siess ldquoFood and cancer state of the art
about the protective effect of fruits and vegetablesrdquo Bulletin duCancer vol 89 no 3 pp 293ndash312 2002
[56] V di Matteo and E Esposito ldquoBiochemical and therapeuticeffects of antioxidants in the treatment of Alzheimerrsquos diseaseParkinsonrsquos disease and amyotrophic lateral sclerosisrdquo CurrentDrug Targets-CNSampNeurological Disorders vol 2 no 2 pp 95ndash107 2003
[57] P Knekt R Jarvinen A Reunanen and J Maatela ldquoFlavonoidintake and coronary mortality in Finland a cohort studyrdquoBritish Medical Journal vol 312 no 7029 pp 478ndash481 1996
[58] R A Mustafa A Abdul Hamid S Mohamed and F A BakarldquoTotal phenolic compounds flavonoids and radical scavengingactivity of 21 selected tropical plantsrdquo Journal of Food Sciencevol 75 no 1 pp C28ndashC35 2010
[59] E B Breidenstein C de la Fuente-Nunez and R E HancockldquoPseudomonas aeruginosa all roads lead to resistancerdquo Trendsin Microbiology vol 19 no 8 pp 419ndash426 2011
[60] C Chu C-H ChiuW-YWu C-H Chu T-P Liu and J T OuldquoLarge drug resistance virulence plasmids of clinical isolates ofSalmonella enterica serovar Choleraesuisrdquo Antimicrobial Agentsand Chemotherapy vol 45 no 8 pp 2299ndash2303 2001
[61] K Hiramatsu H Hanaki T Ino K Yabuta T Oguri andF Tenover ldquoMethicillin-resistant Staphylococcus aureus clini-cal strain with reduced vancomycin susceptibilityrdquo Journal ofAntimicrobial Chemotherapy vol 40 no 1 pp 135ndash136 1997
[62] I TMatsuse Y A LimMHattori M Correa andM P GuptaldquoA search for anti-viral properties in Panamanian medicinalplants the effects on HIV and its essential enzymesrdquo Journal ofEthnopharmacology vol 64 no 1 pp 15ndash22 1998
[63] M Hattori T Nakabayashi Y A Lim et al ldquoInhibitory effectsof various Ayurvedic and Panamanian medicinal plants onthe infection of herpes simplex virus-1 in vitro and in vivordquoPhytotherapy Research vol 9 no 4 pp 270ndash276 1995
[64] I Kola and J Landis ldquoCan the pharmaceutical industry reduceattrition ratesrdquoNature Reviews Drug Discovery vol 3 no 8 pp711ndash716 2004
[65] H Olson G Betton D Robinson et al ldquoConcordance ofthe toxicity of pharmaceuticals in humans and in animalsrdquoRegulatory Toxicology and Pharmacology vol 32 no 1 pp 56ndash67 2000
Fruit Carotenoids Lutein (120573e-carotene-331015840-diol) [26 37]Zeaxanthin (120573120573-carotene-331015840-diol)
Table 5 Percentage ( ww) of mineral contents in the leaves of Pbleo [38]
Mineral elements Percentage weight ()Carbon 506Oxygen 354Magnesium 04Phosphorus 04Sulfur 15Chlorine 12Potassium 102Aluminium NDlowast
Calcium 03Silicon NDFerrum (Iron) NDlowastND not detected
phytoconstituents have been reported in the leaves and twocomponents from the fruit as shown in Table 4 These com-ponents include alkaloids fatty acids glycosides lactonesphenolic sterol terpenoid and carotenoid compounds Themajor isolated component from P bleo leaves is phytol [27]In addition Doetsch et al [34] reported the isolation ofthree alkaloids namely 34-dimethoxy-120573-phenethylamine(mescaline) 3-methoxytyramine and tyramine from theleaves of this plant Vitamin E (120572-tocopherol) [36 37] which
is well known for its antioxidant properties 24-ditert-butylphenol and dihydroactinidiolide were isolated throughbioassay-guided fractionation by Malek et al [36] Murillo etal [26] analyzed the fruit of P bleo for lutein and zeaxanthincontents The total carotenoid content of the fruit was foundto be 133 120583gg making P bleo fruit a high carotenoid foodsource among the wild fruits in Panama
Themineral content of the leaves was also investigated byusing energy-dispersive X-ray microanalysis Table 5 showsthe weight percentage of the minerals reported by Abbde-wahab et al [38] As can be seen P bleo leaves are richin potassium (1016) This is more than two times of thepotassium content of tomato (45) a vegetable known tobe high in potassium [50] It has been shown that a highpotassium diet has an important role in lowering bloodpressure [51] Therefore it might be one of the possiblereasons for the traditional usage of P bleo as a treatment forhypertension [31]
34 Pharmacological Properties Pharmacological evaluationof plants is based on their traditional uses Cancer is oneof the main causes of mortality and morbidity Since Pbleo is traditionally used to prevent and treat cancer [2830 40] it has been most studied for its antiproliferativeand cancer protective properties [8 22 28 32 36 39 40]This is followed by investigations of its antimicrobial andantiparasitic effects in vitro [8 38 41ndash43 52] The snake
Evidence-Based Complementary and Alternative Medicine 5
(a) (b)
(c) (d)
(e) (f)
Figure 1 Photographs of different plant parts of P bleo and P grandifolia (a) Flower of P bleo (b) lower of P grandifolia [47] (c) stem andspines of P bleo (d) stem and spines of P grandifolia [48] (e) ripe fruits and seeds of P bleo and (f) ripe fruits and seeds of P grandifolia [49]
venom neutralizing properties [33] antinociceptive effects[35] and toxicity [22 31] of this plant have been evaluatedthrough in vivo studies
341 Antiproliferative Properties The effects of different Pbleo extracts have been reported on various cell lines in vitroThe crude methanol extract and its ethyl acetate fraction had
significant cytotoxic effects against human nasopharyngealepidermoid carcinoma cell line (KB) [36] In addition theethyl acetate fraction was more active than the methanolextract against human colon carcinoma (HCT116) and hor-mone dependent breast carcinoma cell lines (MCF7) [36]Table 6 shows the reported IC
50values (120583gmL) for the
antiproliferative effects of P bleo extracts and fractions
6 Evidence-Based Complementary and Alternative Medicine
Table6IC
50values
(120583gmL)
ofPbleo
leafextractsandfractio
nson
different
celllin
es
Cellline
Extractsandfractio
ns(IC 5
0120583gmL)
Positivec
ontro
l(IC
50120583
gmL)
Negativec
ontro
lRe
ferences
Methano
lWater
Hexane
Dichlorom
ethane
Ethylacetate
4T1
gt50
gt50
NA
NA
NA
Cisplatin
(NA)
NA
[32]
CasK
i40
5mdash
895
NA
58Doxorub
icin
(6times10minus3)
NA
[36]
CEM-ss
mdashNA
mdashmdash
mdashNA
VC[8]
HT2
9andHCT
116gt30
NA
gt30
gt30
gt30
NA
VC[8]
416
mdash675
NA
22Doxorub
icin
(36times10minus1)
NA
[36]
KB65
mdash28
NA
45
Doxorub
icin
(12times10minus2)
NA
[36]
MCF
-7gt30
NA
gt30
gt30
gt30
NA
VC[8]
39mdash
25NA
28Doxorub
icin
(75times10minus2)
NA
[36]
MRC
-5mdash
mdashmdash
NA
mdashDoxorub
icin
(55times10minus1)
NA
[36]
NIH
3T3
ge200
ge200
NA
NA
NA
Cisplatin
NA
[32]
Saos-2
mdashNA
NA
NA
NA
Cisplatin
NA
[39]
T-47D
2NA
NA
NA
NA
DNaseI
VC[40]
V79
mdashNA
NA
NA
NA
Nitracrin
eVC
[22]
IC5050
ofmaxim
umcellinhibitio
nIC
50lt20120583gmLisconsidered
activ
e100gtIC
50gt20120583gmLisrelativ
elyactiv
eandIC
50gt100isno
tactive[8]
(mdash)no
activ
ity
4T1mou
semam
marycancer
celllin
eCa
sKihu
man
cervicalcarcinom
acelllin
eCE
M-sshu
man
T-4lymph
oblasto
idcelllin
eHT2
9andHCT
116hum
ancoloncarcinom
acelllin
eKB
hum
annasoph
aryn
geal
epidermoidcarcinom
acelllin
eMCF
-7h
ormon
edependent
breastcarcinom
acelllin
eMRC
-5n
ormalhu
man
fibroblastcelllinesN
IH3T3
normalmou
sefib
roblastcelllineSaos-2hum
anosteosarcomacell
lineT-47Dhum
anbreastcarcinom
acelllineV79C
hinese
hamste
rlun
gfib
roblasts
NAnot
available
VCvehiclecontrol
Evidence-Based Complementary and Alternative Medicine 7
Table 7 Reported IC50 values (120583gmL) of selected P bleo phytoconstituents on human cell lines [28]
Compound IC50 (120583gmL) of different cell linesKB MCF7 CasKi HCT 116 A549 MRC-5
Dihydroactinidiolide 67 30 40 5 97 913120573-sitosterol gt100 72 62 gt100 78 gt10024-ditertbutylphenol 081 575 45 29 6 20120572-tocopherol 8 75 6 31 6 305Phytol 71 34 18 100 31 741Mixture of sterols gt100 gt100 gt100 gt100 gt100 gt100Doxorubicin 13 times 10minus2 76 times 10minus2 60 times 10minus3 36 times 10minus1 22 times 10minus1 55 times 10minus1
A549 human lung carcinoma cell line CasKi human cervical carcinoma cell Line HCT116 human colon carcinoma cell Line KB human nasopharyngealepidermoid carcinoma cell Line MCF-7 hormone dependent breast carcinoma cell Line MRC-5 normal human fibroblast cell Lines
Gupta et al [22] reported high tumor inhibition activityin ldquopotato disc inhibition assayrdquo using crown gall tumors(LC5077 ppm)Their result was accompanied by a significant
DNA peak reduction in the DNA intercalation test for themethanol extract of the whole plant
To date no report is available on the in vivo antiprolifer-ative activities of P bleo
(1) Cytotoxic Components Some of the cytotoxic componentsin P bleo have been reported Table 7 shows the reported IC
50
(120583gmL) values of these components in the different humancell lines The effects of these compounds and the mixture ofthe isolated sterols were not as high as doxorubicin that isa chemotherapy drug [28] In another study phytol isolatedfrom P bleo leaves was found to have a significant antitumoractivity against some mouse cancer cell lines [36]
(2) Proposed Antiproliferative Mechanism The antiprolifera-tive activity of the methanol extract of P bleo against humanbreast carcinoma cell line (T-47D) was found to be apoptoticin nature through the activation of caspase-3 and c-mycpathways [40] Caspase-3 and c-myc are frequently activateddeath proteases which catalyze the specific cleavage of manykey cellular proteins They are also essential for normaldevelopment of the tissues as well as apoptosis in the tissuesand cell types [53] Komiya et al [54] reported the inductionof apoptosis as a mechanism of action for cytotoxic activityof phytol DNA intercalation is another proposedmechanismof antiproliferative activity for P bleo [22] However in somestudies P bleo did not show appreciable cytotoxic effect [32]Differences in the sources of plants extractionmethods assaymethods and cell lines can be the possible reasons for thesediscrepancies On the other hand P bleo may contain someprodrugs which are metabolized to the active metabolitesTherefore further studies are needed to better understand itsantiproliferative activity
Apart from the cytotoxic activities against cancer celllines crudemethanol extract and its fractions (hexane waterand ethyl acetate) did not show any cytotoxicity to the normalhuman fibroblast cell lines MRC-5 [36]
342 Antioxidant Activity The adverse effects of oxida-tive stress on human health have become a serious issueOxidative stress causes production of free radicals in thebody that facilitate the development of degenerative diseasessuch as cardiovascular diseases cancers neurodegenerativedisorders [55] Alzheimerrsquos and inflammatory diseases [56]One solution to this problem is to supplement the diet withantioxidant compounds found in natural plant sources [57]Hence in the literature the antioxidant effects of P bleo wereevaluated using different assays as follows
22-Diphenyl-1-picrylhydrazyl Hydrate (DPPH) Assay Themethanol dichloromethane ethyl acetate and hexaneextracts of P bleo leaves were tested [8 25] The hexaneextract exhibited the most effective radical scavengingactivity (EC
50210 120583gmL) followed by the ethyl acetate
extract (EC50
225120583gmL) This spectrophotometric assayuses a stable radical 221015840-diphenylpicrylhydrazyl (DPPH) asa reagent [8 25]
Ferric Reducing Antioxidant Potential Assay (FRAP) Thehexane water and methanol extracts of P bleo leaves werefound to reduce Fe3+ferric cyanide complex to the ferrousform Although the reduction was statistically significant itwas not more than ascorbic acid (vitamin C) and butylatedhydroxyanisole (BHA) as positive controls [25] Hassanba-glou et al [37] compared the antioxidant activity of the ethylacetate extract with that of hexane ethanol and methanolextracts They showed that the ethyl acetate extract hadsignificantly higher antioxidant properties compared to therest of the tested extracts FRAP measures the ability of testsamples to reduce ferric ion to the ferrous form of TPTZ(246-tripyridyl-s-triazine)
120573-Carotene-Linoleic Bleaching AssayThe ethyl acetate extractof P bleo demonstrated the strongest antioxidant activityfollowed by the methanol extract reported by Sim et al [25]In this assay the linoleate free radicals formed during thereaction are neutralized by antioxidants
8 Evidence-Based Complementary and Alternative Medicine
Table8Re
ported
effectsof
Pbleo
extractson
theg
rowth
ofselected
bacteriaandfung
i
Organism
Antibacteria
land
antifun
galeffectof
thee
xtracts
Positivec
ontro
lRe
ferences
Methano
lWater
Hexane
Dichloroethane
Ethylacetate
Chloroform
Bacillussubtilisa
minusNA
minusminus
minusNA
Streptom
ycinlowast
[8]
minusminus
minusNA
minusNA
Gentamicinampicillin
[41]
NA
NA
minusminus
NA
NA
Streptom
ycin
[38]
Escherich
iacolib
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Escherich
iacolia
minusminus
minusNA
minusNA
Gentamicinampicillin
[41]
Helicobacterpylorib
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Klebsiella
pneumoniaeb
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Methicillin
resistant
Staphylococcus
aureus
aminus
NA
minus++
+minus
NA
Streptom
ycinlowast
[8]
NA
NA
minus++
NA
NA
Streptom
ycin
[38]
Mycobacteriu
msm
egmatisb
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Pseudomonas
aeruginosa
a++
NA
+++
++
NA
Streptom
ycin
[8]
+minus
minusNA
+NA
Gentamicinampicillin
[41]
NA
NA
+++
+NA
NA
Streptom
ycinlowast
[38]
Pseudomonas
aeruginosa
bminus
NA
NA
minusNA
NA
Streptom
ycin
[42]
Salm
onellacholeraesuisa
++NA
+++
minusminus
NA
Streptom
ycinlowast
[8]
NA
NA
+++
minusNA
NA
Streptom
ycin
[38]
Staphylococcus
aureus
bminus
NA
NA
minusNA
NA
Streptom
ycin
[42]
Staphylococcus
aureus
aminus
minusminus
NA
minusNA
Gentamicinampicillin
[41]
Cand
idaalbicans
cminus
minusNA
NA
NA
minusProp
icon
azolemicon
azole
[43]
Cand
idaalbicans
bminus
NA
NA
minusNA
NA
Amph
otericin
B[42]
Cladosporiu
mcucumerinum
c+
+NA
NA
NA
+Prop
icon
azolemicon
azole
[43]
a Thes
creening
fora
ntibacteria
leffectwas
carriedou
tbyd
eterminingthez
oneo
finh
ibition
usingpaperd
isc+
stand
sfor
activ
itybetween6ndash
9mm+
+sta
ndsfor
activ
itybetween9ndash
14mm+
++stands
fora
ctivity
morethan14mm
[38]
b (+)
stand
sfor
activ
ityat100120583
gmLforE
coliS
aureusK
pneum
oniaeMsmegmatis
CalbicanceP
aeruginosa
andat125120583gmLforH
pylori(minus)stand
sfor
inactiv
esam
ples
c agaro
verla
yassayand(+)stand
sfor
activ
eextractsa
t50120583
gmL(minus)stand
sfor
inactiv
eextract
NAnot
applicableas
thereisn
orepo
rtin
theliterature
lowastStreptom
ycin
show
ed20
to23
mm
inhibitio
nzoneTh
eresto
fthe
studies
didno
treportthe
exactvalue
oftheinh
ibition
fortheirpo
sitivec
ontro
ls
Evidence-Based Complementary and Alternative Medicine 9
In general although different studies used plant materialsfrom different sources and nonsimilar extraction methodsethyl acetate and hexane extracts appear to be the strongestantioxidant extracts from the P bleo leaves [8 25 37]Moreover this antioxidant capacity is strongly associatedwith the total phenolic compounds and flavonoid content ofthe plant leaves [25 37 58] The above studies suggest thatP bleo has antioxidant properties which can be one of thepossible reasons for its traditional usage for detoxificationand prevention of cancer
343 Antimicrobial Properties P bleo has been shown topossess antibacterial antiviral and antifungal properties invitro Table 8 shows the effect of P bleo extracts on selectedbacteria and fungi As can be seen the methanol andhexane extracts demonstrated great antibacterial activitiesagainst Salmonella choleraesuis and Pseudomonas aeruginosaIn addition its dichloromethane extract showed promisingantibacterial effect againstMethicillin resistant Staphylococcusaureus [8 38] All of the mentioned bacteria are amongthe main causes of nosocomial infections and they havebeen developing antibiotic resistance [59ndash61] Therefore thepotential antibacterial activity of P bleo needs to be furtherinvestigated to identify the lead(s) antibacterial compo-nent(s)
The antifungal activity of the water and methanol extractof P bleo leaves against Cladosporium cucumerinum a plantpathogenic fungus has been reported [43] but they were notactive against Candida albicans a common human pathogen[42 43]
The antiviral properties of the water and methanolextracts of P bleo leaves were evaluated against HerpesSimplex Virus-I (HSV-1) andHuman Immunodeficiency Virus(HIV) by Matsuse et al [62] Both of the extracts demon-strated anti-HIV activity However the result of this studywas not promising because of the low selectivity index of094 Besides in another study by Hattori et al [63] the sameextracts did not demonstrate any antiviral activity againstHSV-1 In general the available data on the antiviral activityof P bleo is neither sufficient nor conclusive Thereforefurther research needs to be carried out
344 Antiparasitic Properties The only antiparasitic inves-tigation on P bleo was reported by Marston et al [52] Intheir study the chloroform methanol and water extractsof this plant did not exert any antiparasitic activity againstschistosomiasis
345 Neutralizing Snake Venom Otero et al [33] evaluatedthe neutralizing effect of the ethanol extract of P bleo onhemorrhagic activity of ldquoBothrops atrox venomrdquo in miceThisextract did not show any neutralizing effect against the testedvenom
346 Antinociceptive Properties Wahab et al [35] evaluatedthe antinociceptive activity of the ethanol extract and itsfractions using two in vivo analgesic models peripheralformalin-induced licking and acetic acid-induced abdominal
writhing They showed that the ethanol extract hexanefraction dichloromethane fraction and ethyl acetate fractionof P bleo had moderate antinociceptive effects However nocompound was identified in their study
35 Toxicity Studies Acute toxicity effect of the leaversquosextracts of P bleo was evaluated by in vitro and in vivostudies Er et al [32] showed that the water extract may formmutagenic compound(s) upon metabolization by the liverenzymes in vitro In another study by Gupta et al [22] themethanol extract of the whole plant had moderate toxicity inbrine shrimp toxicity assay (LD
5077 ppm) In the only in vivo
study by Sim et al [31] the methanol extract did not have anytoxicity effect on ICR mice (LD
50gt 2500mgkg) Although
animalmodels have around 70ndash80 predictability for humantoxicities [64 65] the long term toxicity and themutagenicityof metabolites of P bleo should be further investigated
4 Conclusion
A comprehensive review on Pereskia bleo has been presentedIt provides an overview of the botanical characteristics tra-ditional usage phytoconstituents pharmacological activitiesand safety of P bleo The current review highlights theassociation between the traditional usage of the plant andthe reported anticancer antibacterial and antinociceptiveeffects tested in different studies Although P bleo has beentraditionally used for a variety of therapeutic and prophy-lactic purposes only a few of them has been investigatedHence more research is warranted to further study itsbiological activities and chemical properties to understandits traditional usage and to develop novel therapeuticsUnderstanding the traditional uses knowing the availablescientific evidences and identifying the gaps in research willallow the proper translation of promising research results intoa safe and efficacious usage of herbal medicine and discoveryof new therapeutics It will also assist in setting appropriatepolicy and guidelines in the usage of herbal medicine
Conflict of Interests
All authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgments
Funding from the National University of Singapore (NUS)research Grant (R-148-000-137-112 to KHL) and LeewardPacific Pte Ltd (R-148-000-140-592 to KHL) and researchscholarship from the Singapore International GraduateAward (SINGA SZ) are acknowledged
References
[1] C Wiart Medicinal Plants of Asia and the Pacific Drugs of theFuture World Scientific Singapore 2006
[2] N L Britton and J N Rose The Cactaceae Descriptions andIllustrations of Plants of the Cactus Family Dover PublicationsWashington DC USA 2009
10 Evidence-Based Complementary and Alternative Medicine
[3] E J Edwards and M J Donoghue ldquoPereskia and the origin ofthe cactus life-formrdquo American Naturalist vol 167 no 6 pp777ndash793 2006
[4] E J Edwards R Nyffeler and M J Donoghue ldquoBasal cactusphylogeny implications of Pereskia (Cactaceae) paraphyly forthe transition to the cactus life formrdquo American Journal ofBotany vol 92 no 7 pp 1177ndash1188 2005
[5] R M Ogburn and E J Edwards ldquoAnatomical variation in Cac-taceae and relatives trait lability and evolutionary innovationrdquoAmerican Journal of Botany vol 96 no 2 pp 391ndash408 2009
[6] CM Boo C LOu-Yang andKOmar-Hor 1001Garden Plantsin Singapore National Parks Board Singapore 2nd edition2007
[7] Singapore Npark Board NParks FloraampFouna web 2010httpsflorafaunawebnparksgovsgSpecial-Pagesplant-detailaspxid=2324
[8] S I A Wahab A B Abdul S M Mohan A S Al-Zubairi MM Elhassan andMY Ibrahim ldquoBiological activities ofPereskiableo extractsrdquo International Journal of Pharmacology vol 5 no1 pp 71ndash75 2009
[9] R T Barcenas C Yesson and J A Hawkins ldquoMolecular sys-tematics of the CactaceaerdquoCladistics vol 27 no 5 pp 470ndash4892011
[10] K Y Chong H T Tan and R T Corlett A Checklist of theTotal Vascular Plant Flora of Singapore Native Naturalised andCultivated Species Raffles Museum of Biodiversity ResearchNational University of Singapore Singapore 2009 httprmbrnusedusgraffles museum pubflora of singapore tcpdf
[11] A M Sri Nurestri K S Sim and A W Norhanom ldquoPhy-tochemical and cytotoxic investigations of Pereskia grandifoliaHaw (Cactaceae) leavesrdquo Journal of Biological Sciences vol 9no 5 pp 488ndash493 2009
[12] E Anderson The Cactus Family pp 566ndash568 Timber PressPuritana Ore USA 1st edition 2001
[13] R P Wunderlin and B F Hansen ldquoAtlas of Florida VascularPlantsrdquo 2008 httpwwwplantatlasusfedu
[14] N P Taylor D Zappi P Braun and M Machado ldquoPereskiaaculeata Iucn Red List of Threatened Species Version 2013 2rdquo2013 httpwwwiucnredlistorg
[15] E Pooley A Field Guide to Wild Flowers KwaZulu Natal and theEastern Region Natal Flora Publications Trust Durban SouthAfrica 1999
[16] A G I Natural Heritage Trust ldquoWeedManagementGuide Leafcactus Pereskia aculeatardquo 2003 httpwwwenvironmentgovaubiodiversityinvasiveweedspublicationsguidelinesalertpubsp-aculeatapdf
[18] B E Leuenberger ldquoPereskia Maihuenia and Blossfeldia-taxonomic history updates and notesrdquo Haseltonia no 14 pp54ndash93 2008
[19] J Nugent ldquoPermaculture Plants agaves and cactirdquo 2007 httpbooksgooglecomsgbooksid=YVwMM2OdO34Campq=Pereskia+bleov=snippetampq=Pereskia20bleoampf=false
[20] B E Leuenberger ldquoHumboldt amp Bonplandrsquos Cactaceae in theherbaria at Paris and Berlinrdquo Willdenowia vol 32 pp 137ndash1532002
[21] KA LiamasTropical Flowering Plants AGuide to Identificationand Cultivation Timber Press Portland Ore USA 2003
[22] M P Gupta A Monge G A Karikas et al ldquoScreening of Pana-manian medicinal plants for brine shrimp toxicity crown
gall tumor inhibition cytotoxicity and DNA intercalationrdquoPharmaceutical Biology vol 34 no 1 pp 19ndash27 1996
[23] C C Kazama D T Uchida K N Canzi et al ldquoInvolvementof arginine-vasopressin in the diuretic and hypotensive effectsof Pereskia grandifoliaHaw (Cactaceae)rdquo Journal of Ethnophar-macology vol 144 no 1 pp 86ndash93 2012
[25] K S Sim A M Sri Nurestri and A W Norhanom ldquoPhenoliccontent and antioxidant activity of crude and fractionatedextracts of Pereskia bleo (Kunth) DC (Cactaceae)rdquo AfricanJournal of Pharmacy and Pharmacology vol 4 no 5 pp 193ndash201 2010
[26] EMurillo A JMelendez-Martınez and F Portugal ldquoScreeningof vegetables and fruits from Panama for rich sources of luteinand zeaxanthinrdquo Food Chemistry vol 122 no 1 pp 167ndash1722010
[27] K Hostettmann A Marston M Maillard and M HamburgerPhytochemistry of Plants Used in Traditional Medicine pp 373ndash376 Oxford University Press Oxford UK 1995
[28] S N A Malek S K Shin N A Wahab and H Yaacob ldquoCyto-toxic components of Pereskia bleo (Kunth) DC (Cactaceae)leavesrdquoMolecules vol 14 no 5 pp 1713ndash1724 2009
[29] M P Gupta A Correa DMireya et al ldquoMedicinal plant inven-tory of Kuna Indians part 1rdquo Journal of Ethnopharmacology vol40 no 2 pp 77ndash109 1993
[30] A Rahmat F P Saib and N A Buslima ldquoComparing theeffect of ficus benjamina extract and Pereskia saecnarosa extracton tthe level of micro and macro minerals in normal andinduced liver cancer ratsrdquo in Proceedings of the 4th InternationalConference on Biomedical Engineering in Vietnam pp 208ndash2121980
[31] K S Sim A M Sri Nurestri S K Sinniah K H Kim and AW Norhanom ldquoAcute oral toxicity of Pereskia bleo and Pereskiagrandifolia inmicerdquo PharmacognosyMagazine vol 6 no 21 pp67ndash70 2010
[32] H M Er E Cheng and A K Radhakrishnan ldquoAnti-proliferative and mutagenic activities of aqueous and methanolextracts of leaves from Pereskia bleo (Kunth) DC (Cactaceae)rdquoJournal of Ethnopharmacology vol 113 no 3 pp 448ndash456 2007
[33] R Otero V Nunez J Barona et al ldquoSnakebites and ethnob-otany in the northwest region of Colombia part III neutral-ization of the haemorrhagic effect of Bothrops atrox venomrdquoJournal of Ethnopharmacology vol 73 no 1-2 pp 233ndash2412000
[34] P W Doetsch J M Cassady and J L McLaughlin ldquoCac-tus alkaloids XL Identification of mescaline and other 120573-phenethylamines in Pereskia Pereskiopsis and Islaya by use offluorescamine conjugatesrdquo Journal of Chromatography A vol189 no 1 pp 79ndash85 1980
[35] I R A Wahab C C Guilhon P D Fernandes and F BoylanldquoAnti-nociceptive activity of Pereskia bleo Kunth (Cactaceae)leaves extractsrdquo Journal of Ethnopharmacology vol 144 no 3pp 741ndash746 2012
[36] S N AMalek N AWahabH Yaacob et al ldquoCytotoxic activityof Pereskia bleo (Cactaceae) against selected human cell linesrdquoInternational Journal of Cancer Research vol 4 no 1 pp 20ndash272008
Evidence-Based Complementary and Alternative Medicine 11
[37] B Hassanbaglou A A Hamid A Roheeyati et al ldquoAntioxidantactivity of different extracts from leaves of Pereskia bleo (Cac-taceae)rdquo Journal of Meidinal Plants Research vol 6 no 15 pp2932ndash2937 2012
[38] S I Abbdewahab N M Ain A B Abdul M M E Tahaand T A T Ibrahim ldquoEnergy-dispersive X-raymicroanalysis ofelementsrsquo content and antimicrobial properties of Pereskia bleoandGoniothalamus umbrosusrdquoAfrican Journal of Biotechnologyvol 8 no 10 pp 2375ndash2378 2009
[39] S Y Liew E J Stanbridge K Yusoff and N ShafeeldquoHypoxia affects cellular responses to plant extractsrdquo Journal ofEthnopharmacology vol 144 no 2 pp 453ndash456 2012
[40] M L Tan S F Sulaiman N Najimuddin M R Samian and TS T Muhammad ldquoMethanolic extract of Pereskia bleo (Kunth)DC (Cactaceae) induces apoptosis in breast carcinoma T47-D cell linerdquo Journal of Ethnopharmacology vol 96 no 1-2 pp287ndash294 2005
[41] K Philip S N A Malek W Sani et al ldquoAntimicrobial activityof some medicinal plants from Malaysiardquo American Journal ofApplied Sciences vol 6 no 8 pp 1613ndash1617 2009
[42] T Ruegg A I Calderon E F Queiroz et al ldquo3-farnesyl-2-hydroxybenzoic acid is a new anti-Helicobacter pylori com-pound from Piper multiplinerviumrdquo Journal of Ethnopharma-cology vol 103 no 3 pp 461ndash467 2006
[43] L Rahalison M Hamburger K Hostettmann et al ldquoScreeningfor antifungal activity of Panamanian plantsrdquo InternationalJournal of Pharmacognosy vol 31 no 1 pp 68ndash76 1993
[44] A P D Candolle ldquoPereskia bleo (Kunth) DCrdquo 2011 httpwwwtropicosorgName5100482
[47] M Gardener ldquoTropical plants library onlinerdquo 2014 httpmgonlinecomarticlesexoticsaspx
[48] S Kurt ldquoStem of P grandifoliardquo 2014 httpwwwbiolibde[49] NRCS ldquoNatural Resources and Conservation Service of
USDA Plant profile of P grandifolia Hawrdquo 2013 httpplantsusdagovcoreprofilesymbol=PEGR14
[50] D C Sanders A S Grayson andT JMonaco ldquoMineral contentof tomato (Lycopersicon esculentum) and four competing weedspeciesrdquoWeed Science vol 29 no 5 pp 590ndash593 1981
[51] J M Geleijnse J C Witteman A A Bak J H den Breeijenand D E Grobbee ldquoReduction in blood pressure with a lowsodium high potassium high magnesium salt in older subjectswith mild to moderate hypertensionrdquo British Medical Journalvol 309 no 6952 pp 436ndash440 1994
[52] A Marston G Dudan M P Gupta P N Solis M D Correaand K Hostettmann ldquoScreening of Panamanian plants formolluscicidal activityrdquo Pharmaceutical Biology vol 34 no 1 pp15ndash18 1996
[53] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999
[54] T Komiya M Kyohkon S Ohwaki et al ldquoPhytol inducesprogrammed cell death in human lymphoid leukemia Molt 4Bcellsrdquo International Journal of Molecular Medicine vol 4 no 4pp 377ndash380 1999
[55] M Gerber M C Boutron-Ruault S Hercberg E Riboli AScalbert and M H Siess ldquoFood and cancer state of the art
about the protective effect of fruits and vegetablesrdquo Bulletin duCancer vol 89 no 3 pp 293ndash312 2002
[56] V di Matteo and E Esposito ldquoBiochemical and therapeuticeffects of antioxidants in the treatment of Alzheimerrsquos diseaseParkinsonrsquos disease and amyotrophic lateral sclerosisrdquo CurrentDrug Targets-CNSampNeurological Disorders vol 2 no 2 pp 95ndash107 2003
[57] P Knekt R Jarvinen A Reunanen and J Maatela ldquoFlavonoidintake and coronary mortality in Finland a cohort studyrdquoBritish Medical Journal vol 312 no 7029 pp 478ndash481 1996
[58] R A Mustafa A Abdul Hamid S Mohamed and F A BakarldquoTotal phenolic compounds flavonoids and radical scavengingactivity of 21 selected tropical plantsrdquo Journal of Food Sciencevol 75 no 1 pp C28ndashC35 2010
[59] E B Breidenstein C de la Fuente-Nunez and R E HancockldquoPseudomonas aeruginosa all roads lead to resistancerdquo Trendsin Microbiology vol 19 no 8 pp 419ndash426 2011
[60] C Chu C-H ChiuW-YWu C-H Chu T-P Liu and J T OuldquoLarge drug resistance virulence plasmids of clinical isolates ofSalmonella enterica serovar Choleraesuisrdquo Antimicrobial Agentsand Chemotherapy vol 45 no 8 pp 2299ndash2303 2001
[61] K Hiramatsu H Hanaki T Ino K Yabuta T Oguri andF Tenover ldquoMethicillin-resistant Staphylococcus aureus clini-cal strain with reduced vancomycin susceptibilityrdquo Journal ofAntimicrobial Chemotherapy vol 40 no 1 pp 135ndash136 1997
[62] I TMatsuse Y A LimMHattori M Correa andM P GuptaldquoA search for anti-viral properties in Panamanian medicinalplants the effects on HIV and its essential enzymesrdquo Journal ofEthnopharmacology vol 64 no 1 pp 15ndash22 1998
[63] M Hattori T Nakabayashi Y A Lim et al ldquoInhibitory effectsof various Ayurvedic and Panamanian medicinal plants onthe infection of herpes simplex virus-1 in vitro and in vivordquoPhytotherapy Research vol 9 no 4 pp 270ndash276 1995
[64] I Kola and J Landis ldquoCan the pharmaceutical industry reduceattrition ratesrdquoNature Reviews Drug Discovery vol 3 no 8 pp711ndash716 2004
[65] H Olson G Betton D Robinson et al ldquoConcordance ofthe toxicity of pharmaceuticals in humans and in animalsrdquoRegulatory Toxicology and Pharmacology vol 32 no 1 pp 56ndash67 2000
Evidence-Based Complementary and Alternative Medicine 5
(a) (b)
(c) (d)
(e) (f)
Figure 1 Photographs of different plant parts of P bleo and P grandifolia (a) Flower of P bleo (b) lower of P grandifolia [47] (c) stem andspines of P bleo (d) stem and spines of P grandifolia [48] (e) ripe fruits and seeds of P bleo and (f) ripe fruits and seeds of P grandifolia [49]
venom neutralizing properties [33] antinociceptive effects[35] and toxicity [22 31] of this plant have been evaluatedthrough in vivo studies
341 Antiproliferative Properties The effects of different Pbleo extracts have been reported on various cell lines in vitroThe crude methanol extract and its ethyl acetate fraction had
significant cytotoxic effects against human nasopharyngealepidermoid carcinoma cell line (KB) [36] In addition theethyl acetate fraction was more active than the methanolextract against human colon carcinoma (HCT116) and hor-mone dependent breast carcinoma cell lines (MCF7) [36]Table 6 shows the reported IC
50values (120583gmL) for the
antiproliferative effects of P bleo extracts and fractions
6 Evidence-Based Complementary and Alternative Medicine
Table6IC
50values
(120583gmL)
ofPbleo
leafextractsandfractio
nson
different
celllin
es
Cellline
Extractsandfractio
ns(IC 5
0120583gmL)
Positivec
ontro
l(IC
50120583
gmL)
Negativec
ontro
lRe
ferences
Methano
lWater
Hexane
Dichlorom
ethane
Ethylacetate
4T1
gt50
gt50
NA
NA
NA
Cisplatin
(NA)
NA
[32]
CasK
i40
5mdash
895
NA
58Doxorub
icin
(6times10minus3)
NA
[36]
CEM-ss
mdashNA
mdashmdash
mdashNA
VC[8]
HT2
9andHCT
116gt30
NA
gt30
gt30
gt30
NA
VC[8]
416
mdash675
NA
22Doxorub
icin
(36times10minus1)
NA
[36]
KB65
mdash28
NA
45
Doxorub
icin
(12times10minus2)
NA
[36]
MCF
-7gt30
NA
gt30
gt30
gt30
NA
VC[8]
39mdash
25NA
28Doxorub
icin
(75times10minus2)
NA
[36]
MRC
-5mdash
mdashmdash
NA
mdashDoxorub
icin
(55times10minus1)
NA
[36]
NIH
3T3
ge200
ge200
NA
NA
NA
Cisplatin
NA
[32]
Saos-2
mdashNA
NA
NA
NA
Cisplatin
NA
[39]
T-47D
2NA
NA
NA
NA
DNaseI
VC[40]
V79
mdashNA
NA
NA
NA
Nitracrin
eVC
[22]
IC5050
ofmaxim
umcellinhibitio
nIC
50lt20120583gmLisconsidered
activ
e100gtIC
50gt20120583gmLisrelativ
elyactiv
eandIC
50gt100isno
tactive[8]
(mdash)no
activ
ity
4T1mou
semam
marycancer
celllin
eCa
sKihu
man
cervicalcarcinom
acelllin
eCE
M-sshu
man
T-4lymph
oblasto
idcelllin
eHT2
9andHCT
116hum
ancoloncarcinom
acelllin
eKB
hum
annasoph
aryn
geal
epidermoidcarcinom
acelllin
eMCF
-7h
ormon
edependent
breastcarcinom
acelllin
eMRC
-5n
ormalhu
man
fibroblastcelllinesN
IH3T3
normalmou
sefib
roblastcelllineSaos-2hum
anosteosarcomacell
lineT-47Dhum
anbreastcarcinom
acelllineV79C
hinese
hamste
rlun
gfib
roblasts
NAnot
available
VCvehiclecontrol
Evidence-Based Complementary and Alternative Medicine 7
Table 7 Reported IC50 values (120583gmL) of selected P bleo phytoconstituents on human cell lines [28]
Compound IC50 (120583gmL) of different cell linesKB MCF7 CasKi HCT 116 A549 MRC-5
Dihydroactinidiolide 67 30 40 5 97 913120573-sitosterol gt100 72 62 gt100 78 gt10024-ditertbutylphenol 081 575 45 29 6 20120572-tocopherol 8 75 6 31 6 305Phytol 71 34 18 100 31 741Mixture of sterols gt100 gt100 gt100 gt100 gt100 gt100Doxorubicin 13 times 10minus2 76 times 10minus2 60 times 10minus3 36 times 10minus1 22 times 10minus1 55 times 10minus1
A549 human lung carcinoma cell line CasKi human cervical carcinoma cell Line HCT116 human colon carcinoma cell Line KB human nasopharyngealepidermoid carcinoma cell Line MCF-7 hormone dependent breast carcinoma cell Line MRC-5 normal human fibroblast cell Lines
Gupta et al [22] reported high tumor inhibition activityin ldquopotato disc inhibition assayrdquo using crown gall tumors(LC5077 ppm)Their result was accompanied by a significant
DNA peak reduction in the DNA intercalation test for themethanol extract of the whole plant
To date no report is available on the in vivo antiprolifer-ative activities of P bleo
(1) Cytotoxic Components Some of the cytotoxic componentsin P bleo have been reported Table 7 shows the reported IC
50
(120583gmL) values of these components in the different humancell lines The effects of these compounds and the mixture ofthe isolated sterols were not as high as doxorubicin that isa chemotherapy drug [28] In another study phytol isolatedfrom P bleo leaves was found to have a significant antitumoractivity against some mouse cancer cell lines [36]
(2) Proposed Antiproliferative Mechanism The antiprolifera-tive activity of the methanol extract of P bleo against humanbreast carcinoma cell line (T-47D) was found to be apoptoticin nature through the activation of caspase-3 and c-mycpathways [40] Caspase-3 and c-myc are frequently activateddeath proteases which catalyze the specific cleavage of manykey cellular proteins They are also essential for normaldevelopment of the tissues as well as apoptosis in the tissuesand cell types [53] Komiya et al [54] reported the inductionof apoptosis as a mechanism of action for cytotoxic activityof phytol DNA intercalation is another proposedmechanismof antiproliferative activity for P bleo [22] However in somestudies P bleo did not show appreciable cytotoxic effect [32]Differences in the sources of plants extractionmethods assaymethods and cell lines can be the possible reasons for thesediscrepancies On the other hand P bleo may contain someprodrugs which are metabolized to the active metabolitesTherefore further studies are needed to better understand itsantiproliferative activity
Apart from the cytotoxic activities against cancer celllines crudemethanol extract and its fractions (hexane waterand ethyl acetate) did not show any cytotoxicity to the normalhuman fibroblast cell lines MRC-5 [36]
342 Antioxidant Activity The adverse effects of oxida-tive stress on human health have become a serious issueOxidative stress causes production of free radicals in thebody that facilitate the development of degenerative diseasessuch as cardiovascular diseases cancers neurodegenerativedisorders [55] Alzheimerrsquos and inflammatory diseases [56]One solution to this problem is to supplement the diet withantioxidant compounds found in natural plant sources [57]Hence in the literature the antioxidant effects of P bleo wereevaluated using different assays as follows
22-Diphenyl-1-picrylhydrazyl Hydrate (DPPH) Assay Themethanol dichloromethane ethyl acetate and hexaneextracts of P bleo leaves were tested [8 25] The hexaneextract exhibited the most effective radical scavengingactivity (EC
50210 120583gmL) followed by the ethyl acetate
extract (EC50
225120583gmL) This spectrophotometric assayuses a stable radical 221015840-diphenylpicrylhydrazyl (DPPH) asa reagent [8 25]
Ferric Reducing Antioxidant Potential Assay (FRAP) Thehexane water and methanol extracts of P bleo leaves werefound to reduce Fe3+ferric cyanide complex to the ferrousform Although the reduction was statistically significant itwas not more than ascorbic acid (vitamin C) and butylatedhydroxyanisole (BHA) as positive controls [25] Hassanba-glou et al [37] compared the antioxidant activity of the ethylacetate extract with that of hexane ethanol and methanolextracts They showed that the ethyl acetate extract hadsignificantly higher antioxidant properties compared to therest of the tested extracts FRAP measures the ability of testsamples to reduce ferric ion to the ferrous form of TPTZ(246-tripyridyl-s-triazine)
120573-Carotene-Linoleic Bleaching AssayThe ethyl acetate extractof P bleo demonstrated the strongest antioxidant activityfollowed by the methanol extract reported by Sim et al [25]In this assay the linoleate free radicals formed during thereaction are neutralized by antioxidants
8 Evidence-Based Complementary and Alternative Medicine
Table8Re
ported
effectsof
Pbleo
extractson
theg
rowth
ofselected
bacteriaandfung
i
Organism
Antibacteria
land
antifun
galeffectof
thee
xtracts
Positivec
ontro
lRe
ferences
Methano
lWater
Hexane
Dichloroethane
Ethylacetate
Chloroform
Bacillussubtilisa
minusNA
minusminus
minusNA
Streptom
ycinlowast
[8]
minusminus
minusNA
minusNA
Gentamicinampicillin
[41]
NA
NA
minusminus
NA
NA
Streptom
ycin
[38]
Escherich
iacolib
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Escherich
iacolia
minusminus
minusNA
minusNA
Gentamicinampicillin
[41]
Helicobacterpylorib
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Klebsiella
pneumoniaeb
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Methicillin
resistant
Staphylococcus
aureus
aminus
NA
minus++
+minus
NA
Streptom
ycinlowast
[8]
NA
NA
minus++
NA
NA
Streptom
ycin
[38]
Mycobacteriu
msm
egmatisb
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Pseudomonas
aeruginosa
a++
NA
+++
++
NA
Streptom
ycin
[8]
+minus
minusNA
+NA
Gentamicinampicillin
[41]
NA
NA
+++
+NA
NA
Streptom
ycinlowast
[38]
Pseudomonas
aeruginosa
bminus
NA
NA
minusNA
NA
Streptom
ycin
[42]
Salm
onellacholeraesuisa
++NA
+++
minusminus
NA
Streptom
ycinlowast
[8]
NA
NA
+++
minusNA
NA
Streptom
ycin
[38]
Staphylococcus
aureus
bminus
NA
NA
minusNA
NA
Streptom
ycin
[42]
Staphylococcus
aureus
aminus
minusminus
NA
minusNA
Gentamicinampicillin
[41]
Cand
idaalbicans
cminus
minusNA
NA
NA
minusProp
icon
azolemicon
azole
[43]
Cand
idaalbicans
bminus
NA
NA
minusNA
NA
Amph
otericin
B[42]
Cladosporiu
mcucumerinum
c+
+NA
NA
NA
+Prop
icon
azolemicon
azole
[43]
a Thes
creening
fora
ntibacteria
leffectwas
carriedou
tbyd
eterminingthez
oneo
finh
ibition
usingpaperd
isc+
stand
sfor
activ
itybetween6ndash
9mm+
+sta
ndsfor
activ
itybetween9ndash
14mm+
++stands
fora
ctivity
morethan14mm
[38]
b (+)
stand
sfor
activ
ityat100120583
gmLforE
coliS
aureusK
pneum
oniaeMsmegmatis
CalbicanceP
aeruginosa
andat125120583gmLforH
pylori(minus)stand
sfor
inactiv
esam
ples
c agaro
verla
yassayand(+)stand
sfor
activ
eextractsa
t50120583
gmL(minus)stand
sfor
inactiv
eextract
NAnot
applicableas
thereisn
orepo
rtin
theliterature
lowastStreptom
ycin
show
ed20
to23
mm
inhibitio
nzoneTh
eresto
fthe
studies
didno
treportthe
exactvalue
oftheinh
ibition
fortheirpo
sitivec
ontro
ls
Evidence-Based Complementary and Alternative Medicine 9
In general although different studies used plant materialsfrom different sources and nonsimilar extraction methodsethyl acetate and hexane extracts appear to be the strongestantioxidant extracts from the P bleo leaves [8 25 37]Moreover this antioxidant capacity is strongly associatedwith the total phenolic compounds and flavonoid content ofthe plant leaves [25 37 58] The above studies suggest thatP bleo has antioxidant properties which can be one of thepossible reasons for its traditional usage for detoxificationand prevention of cancer
343 Antimicrobial Properties P bleo has been shown topossess antibacterial antiviral and antifungal properties invitro Table 8 shows the effect of P bleo extracts on selectedbacteria and fungi As can be seen the methanol andhexane extracts demonstrated great antibacterial activitiesagainst Salmonella choleraesuis and Pseudomonas aeruginosaIn addition its dichloromethane extract showed promisingantibacterial effect againstMethicillin resistant Staphylococcusaureus [8 38] All of the mentioned bacteria are amongthe main causes of nosocomial infections and they havebeen developing antibiotic resistance [59ndash61] Therefore thepotential antibacterial activity of P bleo needs to be furtherinvestigated to identify the lead(s) antibacterial compo-nent(s)
The antifungal activity of the water and methanol extractof P bleo leaves against Cladosporium cucumerinum a plantpathogenic fungus has been reported [43] but they were notactive against Candida albicans a common human pathogen[42 43]
The antiviral properties of the water and methanolextracts of P bleo leaves were evaluated against HerpesSimplex Virus-I (HSV-1) andHuman Immunodeficiency Virus(HIV) by Matsuse et al [62] Both of the extracts demon-strated anti-HIV activity However the result of this studywas not promising because of the low selectivity index of094 Besides in another study by Hattori et al [63] the sameextracts did not demonstrate any antiviral activity againstHSV-1 In general the available data on the antiviral activityof P bleo is neither sufficient nor conclusive Thereforefurther research needs to be carried out
344 Antiparasitic Properties The only antiparasitic inves-tigation on P bleo was reported by Marston et al [52] Intheir study the chloroform methanol and water extractsof this plant did not exert any antiparasitic activity againstschistosomiasis
345 Neutralizing Snake Venom Otero et al [33] evaluatedthe neutralizing effect of the ethanol extract of P bleo onhemorrhagic activity of ldquoBothrops atrox venomrdquo in miceThisextract did not show any neutralizing effect against the testedvenom
346 Antinociceptive Properties Wahab et al [35] evaluatedthe antinociceptive activity of the ethanol extract and itsfractions using two in vivo analgesic models peripheralformalin-induced licking and acetic acid-induced abdominal
writhing They showed that the ethanol extract hexanefraction dichloromethane fraction and ethyl acetate fractionof P bleo had moderate antinociceptive effects However nocompound was identified in their study
35 Toxicity Studies Acute toxicity effect of the leaversquosextracts of P bleo was evaluated by in vitro and in vivostudies Er et al [32] showed that the water extract may formmutagenic compound(s) upon metabolization by the liverenzymes in vitro In another study by Gupta et al [22] themethanol extract of the whole plant had moderate toxicity inbrine shrimp toxicity assay (LD
5077 ppm) In the only in vivo
study by Sim et al [31] the methanol extract did not have anytoxicity effect on ICR mice (LD
50gt 2500mgkg) Although
animalmodels have around 70ndash80 predictability for humantoxicities [64 65] the long term toxicity and themutagenicityof metabolites of P bleo should be further investigated
4 Conclusion
A comprehensive review on Pereskia bleo has been presentedIt provides an overview of the botanical characteristics tra-ditional usage phytoconstituents pharmacological activitiesand safety of P bleo The current review highlights theassociation between the traditional usage of the plant andthe reported anticancer antibacterial and antinociceptiveeffects tested in different studies Although P bleo has beentraditionally used for a variety of therapeutic and prophy-lactic purposes only a few of them has been investigatedHence more research is warranted to further study itsbiological activities and chemical properties to understandits traditional usage and to develop novel therapeuticsUnderstanding the traditional uses knowing the availablescientific evidences and identifying the gaps in research willallow the proper translation of promising research results intoa safe and efficacious usage of herbal medicine and discoveryof new therapeutics It will also assist in setting appropriatepolicy and guidelines in the usage of herbal medicine
Conflict of Interests
All authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgments
Funding from the National University of Singapore (NUS)research Grant (R-148-000-137-112 to KHL) and LeewardPacific Pte Ltd (R-148-000-140-592 to KHL) and researchscholarship from the Singapore International GraduateAward (SINGA SZ) are acknowledged
References
[1] C Wiart Medicinal Plants of Asia and the Pacific Drugs of theFuture World Scientific Singapore 2006
[2] N L Britton and J N Rose The Cactaceae Descriptions andIllustrations of Plants of the Cactus Family Dover PublicationsWashington DC USA 2009
10 Evidence-Based Complementary and Alternative Medicine
[3] E J Edwards and M J Donoghue ldquoPereskia and the origin ofthe cactus life-formrdquo American Naturalist vol 167 no 6 pp777ndash793 2006
[4] E J Edwards R Nyffeler and M J Donoghue ldquoBasal cactusphylogeny implications of Pereskia (Cactaceae) paraphyly forthe transition to the cactus life formrdquo American Journal ofBotany vol 92 no 7 pp 1177ndash1188 2005
[5] R M Ogburn and E J Edwards ldquoAnatomical variation in Cac-taceae and relatives trait lability and evolutionary innovationrdquoAmerican Journal of Botany vol 96 no 2 pp 391ndash408 2009
[6] CM Boo C LOu-Yang andKOmar-Hor 1001Garden Plantsin Singapore National Parks Board Singapore 2nd edition2007
[7] Singapore Npark Board NParks FloraampFouna web 2010httpsflorafaunawebnparksgovsgSpecial-Pagesplant-detailaspxid=2324
[8] S I A Wahab A B Abdul S M Mohan A S Al-Zubairi MM Elhassan andMY Ibrahim ldquoBiological activities ofPereskiableo extractsrdquo International Journal of Pharmacology vol 5 no1 pp 71ndash75 2009
[9] R T Barcenas C Yesson and J A Hawkins ldquoMolecular sys-tematics of the CactaceaerdquoCladistics vol 27 no 5 pp 470ndash4892011
[10] K Y Chong H T Tan and R T Corlett A Checklist of theTotal Vascular Plant Flora of Singapore Native Naturalised andCultivated Species Raffles Museum of Biodiversity ResearchNational University of Singapore Singapore 2009 httprmbrnusedusgraffles museum pubflora of singapore tcpdf
[11] A M Sri Nurestri K S Sim and A W Norhanom ldquoPhy-tochemical and cytotoxic investigations of Pereskia grandifoliaHaw (Cactaceae) leavesrdquo Journal of Biological Sciences vol 9no 5 pp 488ndash493 2009
[12] E Anderson The Cactus Family pp 566ndash568 Timber PressPuritana Ore USA 1st edition 2001
[13] R P Wunderlin and B F Hansen ldquoAtlas of Florida VascularPlantsrdquo 2008 httpwwwplantatlasusfedu
[14] N P Taylor D Zappi P Braun and M Machado ldquoPereskiaaculeata Iucn Red List of Threatened Species Version 2013 2rdquo2013 httpwwwiucnredlistorg
[15] E Pooley A Field Guide to Wild Flowers KwaZulu Natal and theEastern Region Natal Flora Publications Trust Durban SouthAfrica 1999
[16] A G I Natural Heritage Trust ldquoWeedManagementGuide Leafcactus Pereskia aculeatardquo 2003 httpwwwenvironmentgovaubiodiversityinvasiveweedspublicationsguidelinesalertpubsp-aculeatapdf
[18] B E Leuenberger ldquoPereskia Maihuenia and Blossfeldia-taxonomic history updates and notesrdquo Haseltonia no 14 pp54ndash93 2008
[19] J Nugent ldquoPermaculture Plants agaves and cactirdquo 2007 httpbooksgooglecomsgbooksid=YVwMM2OdO34Campq=Pereskia+bleov=snippetampq=Pereskia20bleoampf=false
[20] B E Leuenberger ldquoHumboldt amp Bonplandrsquos Cactaceae in theherbaria at Paris and Berlinrdquo Willdenowia vol 32 pp 137ndash1532002
[21] KA LiamasTropical Flowering Plants AGuide to Identificationand Cultivation Timber Press Portland Ore USA 2003
[22] M P Gupta A Monge G A Karikas et al ldquoScreening of Pana-manian medicinal plants for brine shrimp toxicity crown
gall tumor inhibition cytotoxicity and DNA intercalationrdquoPharmaceutical Biology vol 34 no 1 pp 19ndash27 1996
[23] C C Kazama D T Uchida K N Canzi et al ldquoInvolvementof arginine-vasopressin in the diuretic and hypotensive effectsof Pereskia grandifoliaHaw (Cactaceae)rdquo Journal of Ethnophar-macology vol 144 no 1 pp 86ndash93 2012
[25] K S Sim A M Sri Nurestri and A W Norhanom ldquoPhenoliccontent and antioxidant activity of crude and fractionatedextracts of Pereskia bleo (Kunth) DC (Cactaceae)rdquo AfricanJournal of Pharmacy and Pharmacology vol 4 no 5 pp 193ndash201 2010
[26] EMurillo A JMelendez-Martınez and F Portugal ldquoScreeningof vegetables and fruits from Panama for rich sources of luteinand zeaxanthinrdquo Food Chemistry vol 122 no 1 pp 167ndash1722010
[27] K Hostettmann A Marston M Maillard and M HamburgerPhytochemistry of Plants Used in Traditional Medicine pp 373ndash376 Oxford University Press Oxford UK 1995
[28] S N A Malek S K Shin N A Wahab and H Yaacob ldquoCyto-toxic components of Pereskia bleo (Kunth) DC (Cactaceae)leavesrdquoMolecules vol 14 no 5 pp 1713ndash1724 2009
[29] M P Gupta A Correa DMireya et al ldquoMedicinal plant inven-tory of Kuna Indians part 1rdquo Journal of Ethnopharmacology vol40 no 2 pp 77ndash109 1993
[30] A Rahmat F P Saib and N A Buslima ldquoComparing theeffect of ficus benjamina extract and Pereskia saecnarosa extracton tthe level of micro and macro minerals in normal andinduced liver cancer ratsrdquo in Proceedings of the 4th InternationalConference on Biomedical Engineering in Vietnam pp 208ndash2121980
[31] K S Sim A M Sri Nurestri S K Sinniah K H Kim and AW Norhanom ldquoAcute oral toxicity of Pereskia bleo and Pereskiagrandifolia inmicerdquo PharmacognosyMagazine vol 6 no 21 pp67ndash70 2010
[32] H M Er E Cheng and A K Radhakrishnan ldquoAnti-proliferative and mutagenic activities of aqueous and methanolextracts of leaves from Pereskia bleo (Kunth) DC (Cactaceae)rdquoJournal of Ethnopharmacology vol 113 no 3 pp 448ndash456 2007
[33] R Otero V Nunez J Barona et al ldquoSnakebites and ethnob-otany in the northwest region of Colombia part III neutral-ization of the haemorrhagic effect of Bothrops atrox venomrdquoJournal of Ethnopharmacology vol 73 no 1-2 pp 233ndash2412000
[34] P W Doetsch J M Cassady and J L McLaughlin ldquoCac-tus alkaloids XL Identification of mescaline and other 120573-phenethylamines in Pereskia Pereskiopsis and Islaya by use offluorescamine conjugatesrdquo Journal of Chromatography A vol189 no 1 pp 79ndash85 1980
[35] I R A Wahab C C Guilhon P D Fernandes and F BoylanldquoAnti-nociceptive activity of Pereskia bleo Kunth (Cactaceae)leaves extractsrdquo Journal of Ethnopharmacology vol 144 no 3pp 741ndash746 2012
[36] S N AMalek N AWahabH Yaacob et al ldquoCytotoxic activityof Pereskia bleo (Cactaceae) against selected human cell linesrdquoInternational Journal of Cancer Research vol 4 no 1 pp 20ndash272008
Evidence-Based Complementary and Alternative Medicine 11
[37] B Hassanbaglou A A Hamid A Roheeyati et al ldquoAntioxidantactivity of different extracts from leaves of Pereskia bleo (Cac-taceae)rdquo Journal of Meidinal Plants Research vol 6 no 15 pp2932ndash2937 2012
[38] S I Abbdewahab N M Ain A B Abdul M M E Tahaand T A T Ibrahim ldquoEnergy-dispersive X-raymicroanalysis ofelementsrsquo content and antimicrobial properties of Pereskia bleoandGoniothalamus umbrosusrdquoAfrican Journal of Biotechnologyvol 8 no 10 pp 2375ndash2378 2009
[39] S Y Liew E J Stanbridge K Yusoff and N ShafeeldquoHypoxia affects cellular responses to plant extractsrdquo Journal ofEthnopharmacology vol 144 no 2 pp 453ndash456 2012
[40] M L Tan S F Sulaiman N Najimuddin M R Samian and TS T Muhammad ldquoMethanolic extract of Pereskia bleo (Kunth)DC (Cactaceae) induces apoptosis in breast carcinoma T47-D cell linerdquo Journal of Ethnopharmacology vol 96 no 1-2 pp287ndash294 2005
[41] K Philip S N A Malek W Sani et al ldquoAntimicrobial activityof some medicinal plants from Malaysiardquo American Journal ofApplied Sciences vol 6 no 8 pp 1613ndash1617 2009
[42] T Ruegg A I Calderon E F Queiroz et al ldquo3-farnesyl-2-hydroxybenzoic acid is a new anti-Helicobacter pylori com-pound from Piper multiplinerviumrdquo Journal of Ethnopharma-cology vol 103 no 3 pp 461ndash467 2006
[43] L Rahalison M Hamburger K Hostettmann et al ldquoScreeningfor antifungal activity of Panamanian plantsrdquo InternationalJournal of Pharmacognosy vol 31 no 1 pp 68ndash76 1993
[44] A P D Candolle ldquoPereskia bleo (Kunth) DCrdquo 2011 httpwwwtropicosorgName5100482
[47] M Gardener ldquoTropical plants library onlinerdquo 2014 httpmgonlinecomarticlesexoticsaspx
[48] S Kurt ldquoStem of P grandifoliardquo 2014 httpwwwbiolibde[49] NRCS ldquoNatural Resources and Conservation Service of
USDA Plant profile of P grandifolia Hawrdquo 2013 httpplantsusdagovcoreprofilesymbol=PEGR14
[50] D C Sanders A S Grayson andT JMonaco ldquoMineral contentof tomato (Lycopersicon esculentum) and four competing weedspeciesrdquoWeed Science vol 29 no 5 pp 590ndash593 1981
[51] J M Geleijnse J C Witteman A A Bak J H den Breeijenand D E Grobbee ldquoReduction in blood pressure with a lowsodium high potassium high magnesium salt in older subjectswith mild to moderate hypertensionrdquo British Medical Journalvol 309 no 6952 pp 436ndash440 1994
[52] A Marston G Dudan M P Gupta P N Solis M D Correaand K Hostettmann ldquoScreening of Panamanian plants formolluscicidal activityrdquo Pharmaceutical Biology vol 34 no 1 pp15ndash18 1996
[53] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999
[54] T Komiya M Kyohkon S Ohwaki et al ldquoPhytol inducesprogrammed cell death in human lymphoid leukemia Molt 4Bcellsrdquo International Journal of Molecular Medicine vol 4 no 4pp 377ndash380 1999
[55] M Gerber M C Boutron-Ruault S Hercberg E Riboli AScalbert and M H Siess ldquoFood and cancer state of the art
about the protective effect of fruits and vegetablesrdquo Bulletin duCancer vol 89 no 3 pp 293ndash312 2002
[56] V di Matteo and E Esposito ldquoBiochemical and therapeuticeffects of antioxidants in the treatment of Alzheimerrsquos diseaseParkinsonrsquos disease and amyotrophic lateral sclerosisrdquo CurrentDrug Targets-CNSampNeurological Disorders vol 2 no 2 pp 95ndash107 2003
[57] P Knekt R Jarvinen A Reunanen and J Maatela ldquoFlavonoidintake and coronary mortality in Finland a cohort studyrdquoBritish Medical Journal vol 312 no 7029 pp 478ndash481 1996
[58] R A Mustafa A Abdul Hamid S Mohamed and F A BakarldquoTotal phenolic compounds flavonoids and radical scavengingactivity of 21 selected tropical plantsrdquo Journal of Food Sciencevol 75 no 1 pp C28ndashC35 2010
[59] E B Breidenstein C de la Fuente-Nunez and R E HancockldquoPseudomonas aeruginosa all roads lead to resistancerdquo Trendsin Microbiology vol 19 no 8 pp 419ndash426 2011
[60] C Chu C-H ChiuW-YWu C-H Chu T-P Liu and J T OuldquoLarge drug resistance virulence plasmids of clinical isolates ofSalmonella enterica serovar Choleraesuisrdquo Antimicrobial Agentsand Chemotherapy vol 45 no 8 pp 2299ndash2303 2001
[61] K Hiramatsu H Hanaki T Ino K Yabuta T Oguri andF Tenover ldquoMethicillin-resistant Staphylococcus aureus clini-cal strain with reduced vancomycin susceptibilityrdquo Journal ofAntimicrobial Chemotherapy vol 40 no 1 pp 135ndash136 1997
[62] I TMatsuse Y A LimMHattori M Correa andM P GuptaldquoA search for anti-viral properties in Panamanian medicinalplants the effects on HIV and its essential enzymesrdquo Journal ofEthnopharmacology vol 64 no 1 pp 15ndash22 1998
[63] M Hattori T Nakabayashi Y A Lim et al ldquoInhibitory effectsof various Ayurvedic and Panamanian medicinal plants onthe infection of herpes simplex virus-1 in vitro and in vivordquoPhytotherapy Research vol 9 no 4 pp 270ndash276 1995
[64] I Kola and J Landis ldquoCan the pharmaceutical industry reduceattrition ratesrdquoNature Reviews Drug Discovery vol 3 no 8 pp711ndash716 2004
[65] H Olson G Betton D Robinson et al ldquoConcordance ofthe toxicity of pharmaceuticals in humans and in animalsrdquoRegulatory Toxicology and Pharmacology vol 32 no 1 pp 56ndash67 2000
6 Evidence-Based Complementary and Alternative Medicine
Table6IC
50values
(120583gmL)
ofPbleo
leafextractsandfractio
nson
different
celllin
es
Cellline
Extractsandfractio
ns(IC 5
0120583gmL)
Positivec
ontro
l(IC
50120583
gmL)
Negativec
ontro
lRe
ferences
Methano
lWater
Hexane
Dichlorom
ethane
Ethylacetate
4T1
gt50
gt50
NA
NA
NA
Cisplatin
(NA)
NA
[32]
CasK
i40
5mdash
895
NA
58Doxorub
icin
(6times10minus3)
NA
[36]
CEM-ss
mdashNA
mdashmdash
mdashNA
VC[8]
HT2
9andHCT
116gt30
NA
gt30
gt30
gt30
NA
VC[8]
416
mdash675
NA
22Doxorub
icin
(36times10minus1)
NA
[36]
KB65
mdash28
NA
45
Doxorub
icin
(12times10minus2)
NA
[36]
MCF
-7gt30
NA
gt30
gt30
gt30
NA
VC[8]
39mdash
25NA
28Doxorub
icin
(75times10minus2)
NA
[36]
MRC
-5mdash
mdashmdash
NA
mdashDoxorub
icin
(55times10minus1)
NA
[36]
NIH
3T3
ge200
ge200
NA
NA
NA
Cisplatin
NA
[32]
Saos-2
mdashNA
NA
NA
NA
Cisplatin
NA
[39]
T-47D
2NA
NA
NA
NA
DNaseI
VC[40]
V79
mdashNA
NA
NA
NA
Nitracrin
eVC
[22]
IC5050
ofmaxim
umcellinhibitio
nIC
50lt20120583gmLisconsidered
activ
e100gtIC
50gt20120583gmLisrelativ
elyactiv
eandIC
50gt100isno
tactive[8]
(mdash)no
activ
ity
4T1mou
semam
marycancer
celllin
eCa
sKihu
man
cervicalcarcinom
acelllin
eCE
M-sshu
man
T-4lymph
oblasto
idcelllin
eHT2
9andHCT
116hum
ancoloncarcinom
acelllin
eKB
hum
annasoph
aryn
geal
epidermoidcarcinom
acelllin
eMCF
-7h
ormon
edependent
breastcarcinom
acelllin
eMRC
-5n
ormalhu
man
fibroblastcelllinesN
IH3T3
normalmou
sefib
roblastcelllineSaos-2hum
anosteosarcomacell
lineT-47Dhum
anbreastcarcinom
acelllineV79C
hinese
hamste
rlun
gfib
roblasts
NAnot
available
VCvehiclecontrol
Evidence-Based Complementary and Alternative Medicine 7
Table 7 Reported IC50 values (120583gmL) of selected P bleo phytoconstituents on human cell lines [28]
Compound IC50 (120583gmL) of different cell linesKB MCF7 CasKi HCT 116 A549 MRC-5
Dihydroactinidiolide 67 30 40 5 97 913120573-sitosterol gt100 72 62 gt100 78 gt10024-ditertbutylphenol 081 575 45 29 6 20120572-tocopherol 8 75 6 31 6 305Phytol 71 34 18 100 31 741Mixture of sterols gt100 gt100 gt100 gt100 gt100 gt100Doxorubicin 13 times 10minus2 76 times 10minus2 60 times 10minus3 36 times 10minus1 22 times 10minus1 55 times 10minus1
A549 human lung carcinoma cell line CasKi human cervical carcinoma cell Line HCT116 human colon carcinoma cell Line KB human nasopharyngealepidermoid carcinoma cell Line MCF-7 hormone dependent breast carcinoma cell Line MRC-5 normal human fibroblast cell Lines
Gupta et al [22] reported high tumor inhibition activityin ldquopotato disc inhibition assayrdquo using crown gall tumors(LC5077 ppm)Their result was accompanied by a significant
DNA peak reduction in the DNA intercalation test for themethanol extract of the whole plant
To date no report is available on the in vivo antiprolifer-ative activities of P bleo
(1) Cytotoxic Components Some of the cytotoxic componentsin P bleo have been reported Table 7 shows the reported IC
50
(120583gmL) values of these components in the different humancell lines The effects of these compounds and the mixture ofthe isolated sterols were not as high as doxorubicin that isa chemotherapy drug [28] In another study phytol isolatedfrom P bleo leaves was found to have a significant antitumoractivity against some mouse cancer cell lines [36]
(2) Proposed Antiproliferative Mechanism The antiprolifera-tive activity of the methanol extract of P bleo against humanbreast carcinoma cell line (T-47D) was found to be apoptoticin nature through the activation of caspase-3 and c-mycpathways [40] Caspase-3 and c-myc are frequently activateddeath proteases which catalyze the specific cleavage of manykey cellular proteins They are also essential for normaldevelopment of the tissues as well as apoptosis in the tissuesand cell types [53] Komiya et al [54] reported the inductionof apoptosis as a mechanism of action for cytotoxic activityof phytol DNA intercalation is another proposedmechanismof antiproliferative activity for P bleo [22] However in somestudies P bleo did not show appreciable cytotoxic effect [32]Differences in the sources of plants extractionmethods assaymethods and cell lines can be the possible reasons for thesediscrepancies On the other hand P bleo may contain someprodrugs which are metabolized to the active metabolitesTherefore further studies are needed to better understand itsantiproliferative activity
Apart from the cytotoxic activities against cancer celllines crudemethanol extract and its fractions (hexane waterand ethyl acetate) did not show any cytotoxicity to the normalhuman fibroblast cell lines MRC-5 [36]
342 Antioxidant Activity The adverse effects of oxida-tive stress on human health have become a serious issueOxidative stress causes production of free radicals in thebody that facilitate the development of degenerative diseasessuch as cardiovascular diseases cancers neurodegenerativedisorders [55] Alzheimerrsquos and inflammatory diseases [56]One solution to this problem is to supplement the diet withantioxidant compounds found in natural plant sources [57]Hence in the literature the antioxidant effects of P bleo wereevaluated using different assays as follows
22-Diphenyl-1-picrylhydrazyl Hydrate (DPPH) Assay Themethanol dichloromethane ethyl acetate and hexaneextracts of P bleo leaves were tested [8 25] The hexaneextract exhibited the most effective radical scavengingactivity (EC
50210 120583gmL) followed by the ethyl acetate
extract (EC50
225120583gmL) This spectrophotometric assayuses a stable radical 221015840-diphenylpicrylhydrazyl (DPPH) asa reagent [8 25]
Ferric Reducing Antioxidant Potential Assay (FRAP) Thehexane water and methanol extracts of P bleo leaves werefound to reduce Fe3+ferric cyanide complex to the ferrousform Although the reduction was statistically significant itwas not more than ascorbic acid (vitamin C) and butylatedhydroxyanisole (BHA) as positive controls [25] Hassanba-glou et al [37] compared the antioxidant activity of the ethylacetate extract with that of hexane ethanol and methanolextracts They showed that the ethyl acetate extract hadsignificantly higher antioxidant properties compared to therest of the tested extracts FRAP measures the ability of testsamples to reduce ferric ion to the ferrous form of TPTZ(246-tripyridyl-s-triazine)
120573-Carotene-Linoleic Bleaching AssayThe ethyl acetate extractof P bleo demonstrated the strongest antioxidant activityfollowed by the methanol extract reported by Sim et al [25]In this assay the linoleate free radicals formed during thereaction are neutralized by antioxidants
8 Evidence-Based Complementary and Alternative Medicine
Table8Re
ported
effectsof
Pbleo
extractson
theg
rowth
ofselected
bacteriaandfung
i
Organism
Antibacteria
land
antifun
galeffectof
thee
xtracts
Positivec
ontro
lRe
ferences
Methano
lWater
Hexane
Dichloroethane
Ethylacetate
Chloroform
Bacillussubtilisa
minusNA
minusminus
minusNA
Streptom
ycinlowast
[8]
minusminus
minusNA
minusNA
Gentamicinampicillin
[41]
NA
NA
minusminus
NA
NA
Streptom
ycin
[38]
Escherich
iacolib
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Escherich
iacolia
minusminus
minusNA
minusNA
Gentamicinampicillin
[41]
Helicobacterpylorib
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Klebsiella
pneumoniaeb
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Methicillin
resistant
Staphylococcus
aureus
aminus
NA
minus++
+minus
NA
Streptom
ycinlowast
[8]
NA
NA
minus++
NA
NA
Streptom
ycin
[38]
Mycobacteriu
msm
egmatisb
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Pseudomonas
aeruginosa
a++
NA
+++
++
NA
Streptom
ycin
[8]
+minus
minusNA
+NA
Gentamicinampicillin
[41]
NA
NA
+++
+NA
NA
Streptom
ycinlowast
[38]
Pseudomonas
aeruginosa
bminus
NA
NA
minusNA
NA
Streptom
ycin
[42]
Salm
onellacholeraesuisa
++NA
+++
minusminus
NA
Streptom
ycinlowast
[8]
NA
NA
+++
minusNA
NA
Streptom
ycin
[38]
Staphylococcus
aureus
bminus
NA
NA
minusNA
NA
Streptom
ycin
[42]
Staphylococcus
aureus
aminus
minusminus
NA
minusNA
Gentamicinampicillin
[41]
Cand
idaalbicans
cminus
minusNA
NA
NA
minusProp
icon
azolemicon
azole
[43]
Cand
idaalbicans
bminus
NA
NA
minusNA
NA
Amph
otericin
B[42]
Cladosporiu
mcucumerinum
c+
+NA
NA
NA
+Prop
icon
azolemicon
azole
[43]
a Thes
creening
fora
ntibacteria
leffectwas
carriedou
tbyd
eterminingthez
oneo
finh
ibition
usingpaperd
isc+
stand
sfor
activ
itybetween6ndash
9mm+
+sta
ndsfor
activ
itybetween9ndash
14mm+
++stands
fora
ctivity
morethan14mm
[38]
b (+)
stand
sfor
activ
ityat100120583
gmLforE
coliS
aureusK
pneum
oniaeMsmegmatis
CalbicanceP
aeruginosa
andat125120583gmLforH
pylori(minus)stand
sfor
inactiv
esam
ples
c agaro
verla
yassayand(+)stand
sfor
activ
eextractsa
t50120583
gmL(minus)stand
sfor
inactiv
eextract
NAnot
applicableas
thereisn
orepo
rtin
theliterature
lowastStreptom
ycin
show
ed20
to23
mm
inhibitio
nzoneTh
eresto
fthe
studies
didno
treportthe
exactvalue
oftheinh
ibition
fortheirpo
sitivec
ontro
ls
Evidence-Based Complementary and Alternative Medicine 9
In general although different studies used plant materialsfrom different sources and nonsimilar extraction methodsethyl acetate and hexane extracts appear to be the strongestantioxidant extracts from the P bleo leaves [8 25 37]Moreover this antioxidant capacity is strongly associatedwith the total phenolic compounds and flavonoid content ofthe plant leaves [25 37 58] The above studies suggest thatP bleo has antioxidant properties which can be one of thepossible reasons for its traditional usage for detoxificationand prevention of cancer
343 Antimicrobial Properties P bleo has been shown topossess antibacterial antiviral and antifungal properties invitro Table 8 shows the effect of P bleo extracts on selectedbacteria and fungi As can be seen the methanol andhexane extracts demonstrated great antibacterial activitiesagainst Salmonella choleraesuis and Pseudomonas aeruginosaIn addition its dichloromethane extract showed promisingantibacterial effect againstMethicillin resistant Staphylococcusaureus [8 38] All of the mentioned bacteria are amongthe main causes of nosocomial infections and they havebeen developing antibiotic resistance [59ndash61] Therefore thepotential antibacterial activity of P bleo needs to be furtherinvestigated to identify the lead(s) antibacterial compo-nent(s)
The antifungal activity of the water and methanol extractof P bleo leaves against Cladosporium cucumerinum a plantpathogenic fungus has been reported [43] but they were notactive against Candida albicans a common human pathogen[42 43]
The antiviral properties of the water and methanolextracts of P bleo leaves were evaluated against HerpesSimplex Virus-I (HSV-1) andHuman Immunodeficiency Virus(HIV) by Matsuse et al [62] Both of the extracts demon-strated anti-HIV activity However the result of this studywas not promising because of the low selectivity index of094 Besides in another study by Hattori et al [63] the sameextracts did not demonstrate any antiviral activity againstHSV-1 In general the available data on the antiviral activityof P bleo is neither sufficient nor conclusive Thereforefurther research needs to be carried out
344 Antiparasitic Properties The only antiparasitic inves-tigation on P bleo was reported by Marston et al [52] Intheir study the chloroform methanol and water extractsof this plant did not exert any antiparasitic activity againstschistosomiasis
345 Neutralizing Snake Venom Otero et al [33] evaluatedthe neutralizing effect of the ethanol extract of P bleo onhemorrhagic activity of ldquoBothrops atrox venomrdquo in miceThisextract did not show any neutralizing effect against the testedvenom
346 Antinociceptive Properties Wahab et al [35] evaluatedthe antinociceptive activity of the ethanol extract and itsfractions using two in vivo analgesic models peripheralformalin-induced licking and acetic acid-induced abdominal
writhing They showed that the ethanol extract hexanefraction dichloromethane fraction and ethyl acetate fractionof P bleo had moderate antinociceptive effects However nocompound was identified in their study
35 Toxicity Studies Acute toxicity effect of the leaversquosextracts of P bleo was evaluated by in vitro and in vivostudies Er et al [32] showed that the water extract may formmutagenic compound(s) upon metabolization by the liverenzymes in vitro In another study by Gupta et al [22] themethanol extract of the whole plant had moderate toxicity inbrine shrimp toxicity assay (LD
5077 ppm) In the only in vivo
study by Sim et al [31] the methanol extract did not have anytoxicity effect on ICR mice (LD
50gt 2500mgkg) Although
animalmodels have around 70ndash80 predictability for humantoxicities [64 65] the long term toxicity and themutagenicityof metabolites of P bleo should be further investigated
4 Conclusion
A comprehensive review on Pereskia bleo has been presentedIt provides an overview of the botanical characteristics tra-ditional usage phytoconstituents pharmacological activitiesand safety of P bleo The current review highlights theassociation between the traditional usage of the plant andthe reported anticancer antibacterial and antinociceptiveeffects tested in different studies Although P bleo has beentraditionally used for a variety of therapeutic and prophy-lactic purposes only a few of them has been investigatedHence more research is warranted to further study itsbiological activities and chemical properties to understandits traditional usage and to develop novel therapeuticsUnderstanding the traditional uses knowing the availablescientific evidences and identifying the gaps in research willallow the proper translation of promising research results intoa safe and efficacious usage of herbal medicine and discoveryof new therapeutics It will also assist in setting appropriatepolicy and guidelines in the usage of herbal medicine
Conflict of Interests
All authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgments
Funding from the National University of Singapore (NUS)research Grant (R-148-000-137-112 to KHL) and LeewardPacific Pte Ltd (R-148-000-140-592 to KHL) and researchscholarship from the Singapore International GraduateAward (SINGA SZ) are acknowledged
References
[1] C Wiart Medicinal Plants of Asia and the Pacific Drugs of theFuture World Scientific Singapore 2006
[2] N L Britton and J N Rose The Cactaceae Descriptions andIllustrations of Plants of the Cactus Family Dover PublicationsWashington DC USA 2009
10 Evidence-Based Complementary and Alternative Medicine
[3] E J Edwards and M J Donoghue ldquoPereskia and the origin ofthe cactus life-formrdquo American Naturalist vol 167 no 6 pp777ndash793 2006
[4] E J Edwards R Nyffeler and M J Donoghue ldquoBasal cactusphylogeny implications of Pereskia (Cactaceae) paraphyly forthe transition to the cactus life formrdquo American Journal ofBotany vol 92 no 7 pp 1177ndash1188 2005
[5] R M Ogburn and E J Edwards ldquoAnatomical variation in Cac-taceae and relatives trait lability and evolutionary innovationrdquoAmerican Journal of Botany vol 96 no 2 pp 391ndash408 2009
[6] CM Boo C LOu-Yang andKOmar-Hor 1001Garden Plantsin Singapore National Parks Board Singapore 2nd edition2007
[7] Singapore Npark Board NParks FloraampFouna web 2010httpsflorafaunawebnparksgovsgSpecial-Pagesplant-detailaspxid=2324
[8] S I A Wahab A B Abdul S M Mohan A S Al-Zubairi MM Elhassan andMY Ibrahim ldquoBiological activities ofPereskiableo extractsrdquo International Journal of Pharmacology vol 5 no1 pp 71ndash75 2009
[9] R T Barcenas C Yesson and J A Hawkins ldquoMolecular sys-tematics of the CactaceaerdquoCladistics vol 27 no 5 pp 470ndash4892011
[10] K Y Chong H T Tan and R T Corlett A Checklist of theTotal Vascular Plant Flora of Singapore Native Naturalised andCultivated Species Raffles Museum of Biodiversity ResearchNational University of Singapore Singapore 2009 httprmbrnusedusgraffles museum pubflora of singapore tcpdf
[11] A M Sri Nurestri K S Sim and A W Norhanom ldquoPhy-tochemical and cytotoxic investigations of Pereskia grandifoliaHaw (Cactaceae) leavesrdquo Journal of Biological Sciences vol 9no 5 pp 488ndash493 2009
[12] E Anderson The Cactus Family pp 566ndash568 Timber PressPuritana Ore USA 1st edition 2001
[13] R P Wunderlin and B F Hansen ldquoAtlas of Florida VascularPlantsrdquo 2008 httpwwwplantatlasusfedu
[14] N P Taylor D Zappi P Braun and M Machado ldquoPereskiaaculeata Iucn Red List of Threatened Species Version 2013 2rdquo2013 httpwwwiucnredlistorg
[15] E Pooley A Field Guide to Wild Flowers KwaZulu Natal and theEastern Region Natal Flora Publications Trust Durban SouthAfrica 1999
[16] A G I Natural Heritage Trust ldquoWeedManagementGuide Leafcactus Pereskia aculeatardquo 2003 httpwwwenvironmentgovaubiodiversityinvasiveweedspublicationsguidelinesalertpubsp-aculeatapdf
[18] B E Leuenberger ldquoPereskia Maihuenia and Blossfeldia-taxonomic history updates and notesrdquo Haseltonia no 14 pp54ndash93 2008
[19] J Nugent ldquoPermaculture Plants agaves and cactirdquo 2007 httpbooksgooglecomsgbooksid=YVwMM2OdO34Campq=Pereskia+bleov=snippetampq=Pereskia20bleoampf=false
[20] B E Leuenberger ldquoHumboldt amp Bonplandrsquos Cactaceae in theherbaria at Paris and Berlinrdquo Willdenowia vol 32 pp 137ndash1532002
[21] KA LiamasTropical Flowering Plants AGuide to Identificationand Cultivation Timber Press Portland Ore USA 2003
[22] M P Gupta A Monge G A Karikas et al ldquoScreening of Pana-manian medicinal plants for brine shrimp toxicity crown
gall tumor inhibition cytotoxicity and DNA intercalationrdquoPharmaceutical Biology vol 34 no 1 pp 19ndash27 1996
[23] C C Kazama D T Uchida K N Canzi et al ldquoInvolvementof arginine-vasopressin in the diuretic and hypotensive effectsof Pereskia grandifoliaHaw (Cactaceae)rdquo Journal of Ethnophar-macology vol 144 no 1 pp 86ndash93 2012
[25] K S Sim A M Sri Nurestri and A W Norhanom ldquoPhenoliccontent and antioxidant activity of crude and fractionatedextracts of Pereskia bleo (Kunth) DC (Cactaceae)rdquo AfricanJournal of Pharmacy and Pharmacology vol 4 no 5 pp 193ndash201 2010
[26] EMurillo A JMelendez-Martınez and F Portugal ldquoScreeningof vegetables and fruits from Panama for rich sources of luteinand zeaxanthinrdquo Food Chemistry vol 122 no 1 pp 167ndash1722010
[27] K Hostettmann A Marston M Maillard and M HamburgerPhytochemistry of Plants Used in Traditional Medicine pp 373ndash376 Oxford University Press Oxford UK 1995
[28] S N A Malek S K Shin N A Wahab and H Yaacob ldquoCyto-toxic components of Pereskia bleo (Kunth) DC (Cactaceae)leavesrdquoMolecules vol 14 no 5 pp 1713ndash1724 2009
[29] M P Gupta A Correa DMireya et al ldquoMedicinal plant inven-tory of Kuna Indians part 1rdquo Journal of Ethnopharmacology vol40 no 2 pp 77ndash109 1993
[30] A Rahmat F P Saib and N A Buslima ldquoComparing theeffect of ficus benjamina extract and Pereskia saecnarosa extracton tthe level of micro and macro minerals in normal andinduced liver cancer ratsrdquo in Proceedings of the 4th InternationalConference on Biomedical Engineering in Vietnam pp 208ndash2121980
[31] K S Sim A M Sri Nurestri S K Sinniah K H Kim and AW Norhanom ldquoAcute oral toxicity of Pereskia bleo and Pereskiagrandifolia inmicerdquo PharmacognosyMagazine vol 6 no 21 pp67ndash70 2010
[32] H M Er E Cheng and A K Radhakrishnan ldquoAnti-proliferative and mutagenic activities of aqueous and methanolextracts of leaves from Pereskia bleo (Kunth) DC (Cactaceae)rdquoJournal of Ethnopharmacology vol 113 no 3 pp 448ndash456 2007
[33] R Otero V Nunez J Barona et al ldquoSnakebites and ethnob-otany in the northwest region of Colombia part III neutral-ization of the haemorrhagic effect of Bothrops atrox venomrdquoJournal of Ethnopharmacology vol 73 no 1-2 pp 233ndash2412000
[34] P W Doetsch J M Cassady and J L McLaughlin ldquoCac-tus alkaloids XL Identification of mescaline and other 120573-phenethylamines in Pereskia Pereskiopsis and Islaya by use offluorescamine conjugatesrdquo Journal of Chromatography A vol189 no 1 pp 79ndash85 1980
[35] I R A Wahab C C Guilhon P D Fernandes and F BoylanldquoAnti-nociceptive activity of Pereskia bleo Kunth (Cactaceae)leaves extractsrdquo Journal of Ethnopharmacology vol 144 no 3pp 741ndash746 2012
[36] S N AMalek N AWahabH Yaacob et al ldquoCytotoxic activityof Pereskia bleo (Cactaceae) against selected human cell linesrdquoInternational Journal of Cancer Research vol 4 no 1 pp 20ndash272008
Evidence-Based Complementary and Alternative Medicine 11
[37] B Hassanbaglou A A Hamid A Roheeyati et al ldquoAntioxidantactivity of different extracts from leaves of Pereskia bleo (Cac-taceae)rdquo Journal of Meidinal Plants Research vol 6 no 15 pp2932ndash2937 2012
[38] S I Abbdewahab N M Ain A B Abdul M M E Tahaand T A T Ibrahim ldquoEnergy-dispersive X-raymicroanalysis ofelementsrsquo content and antimicrobial properties of Pereskia bleoandGoniothalamus umbrosusrdquoAfrican Journal of Biotechnologyvol 8 no 10 pp 2375ndash2378 2009
[39] S Y Liew E J Stanbridge K Yusoff and N ShafeeldquoHypoxia affects cellular responses to plant extractsrdquo Journal ofEthnopharmacology vol 144 no 2 pp 453ndash456 2012
[40] M L Tan S F Sulaiman N Najimuddin M R Samian and TS T Muhammad ldquoMethanolic extract of Pereskia bleo (Kunth)DC (Cactaceae) induces apoptosis in breast carcinoma T47-D cell linerdquo Journal of Ethnopharmacology vol 96 no 1-2 pp287ndash294 2005
[41] K Philip S N A Malek W Sani et al ldquoAntimicrobial activityof some medicinal plants from Malaysiardquo American Journal ofApplied Sciences vol 6 no 8 pp 1613ndash1617 2009
[42] T Ruegg A I Calderon E F Queiroz et al ldquo3-farnesyl-2-hydroxybenzoic acid is a new anti-Helicobacter pylori com-pound from Piper multiplinerviumrdquo Journal of Ethnopharma-cology vol 103 no 3 pp 461ndash467 2006
[43] L Rahalison M Hamburger K Hostettmann et al ldquoScreeningfor antifungal activity of Panamanian plantsrdquo InternationalJournal of Pharmacognosy vol 31 no 1 pp 68ndash76 1993
[44] A P D Candolle ldquoPereskia bleo (Kunth) DCrdquo 2011 httpwwwtropicosorgName5100482
[47] M Gardener ldquoTropical plants library onlinerdquo 2014 httpmgonlinecomarticlesexoticsaspx
[48] S Kurt ldquoStem of P grandifoliardquo 2014 httpwwwbiolibde[49] NRCS ldquoNatural Resources and Conservation Service of
USDA Plant profile of P grandifolia Hawrdquo 2013 httpplantsusdagovcoreprofilesymbol=PEGR14
[50] D C Sanders A S Grayson andT JMonaco ldquoMineral contentof tomato (Lycopersicon esculentum) and four competing weedspeciesrdquoWeed Science vol 29 no 5 pp 590ndash593 1981
[51] J M Geleijnse J C Witteman A A Bak J H den Breeijenand D E Grobbee ldquoReduction in blood pressure with a lowsodium high potassium high magnesium salt in older subjectswith mild to moderate hypertensionrdquo British Medical Journalvol 309 no 6952 pp 436ndash440 1994
[52] A Marston G Dudan M P Gupta P N Solis M D Correaand K Hostettmann ldquoScreening of Panamanian plants formolluscicidal activityrdquo Pharmaceutical Biology vol 34 no 1 pp15ndash18 1996
[53] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999
[54] T Komiya M Kyohkon S Ohwaki et al ldquoPhytol inducesprogrammed cell death in human lymphoid leukemia Molt 4Bcellsrdquo International Journal of Molecular Medicine vol 4 no 4pp 377ndash380 1999
[55] M Gerber M C Boutron-Ruault S Hercberg E Riboli AScalbert and M H Siess ldquoFood and cancer state of the art
about the protective effect of fruits and vegetablesrdquo Bulletin duCancer vol 89 no 3 pp 293ndash312 2002
[56] V di Matteo and E Esposito ldquoBiochemical and therapeuticeffects of antioxidants in the treatment of Alzheimerrsquos diseaseParkinsonrsquos disease and amyotrophic lateral sclerosisrdquo CurrentDrug Targets-CNSampNeurological Disorders vol 2 no 2 pp 95ndash107 2003
[57] P Knekt R Jarvinen A Reunanen and J Maatela ldquoFlavonoidintake and coronary mortality in Finland a cohort studyrdquoBritish Medical Journal vol 312 no 7029 pp 478ndash481 1996
[58] R A Mustafa A Abdul Hamid S Mohamed and F A BakarldquoTotal phenolic compounds flavonoids and radical scavengingactivity of 21 selected tropical plantsrdquo Journal of Food Sciencevol 75 no 1 pp C28ndashC35 2010
[59] E B Breidenstein C de la Fuente-Nunez and R E HancockldquoPseudomonas aeruginosa all roads lead to resistancerdquo Trendsin Microbiology vol 19 no 8 pp 419ndash426 2011
[60] C Chu C-H ChiuW-YWu C-H Chu T-P Liu and J T OuldquoLarge drug resistance virulence plasmids of clinical isolates ofSalmonella enterica serovar Choleraesuisrdquo Antimicrobial Agentsand Chemotherapy vol 45 no 8 pp 2299ndash2303 2001
[61] K Hiramatsu H Hanaki T Ino K Yabuta T Oguri andF Tenover ldquoMethicillin-resistant Staphylococcus aureus clini-cal strain with reduced vancomycin susceptibilityrdquo Journal ofAntimicrobial Chemotherapy vol 40 no 1 pp 135ndash136 1997
[62] I TMatsuse Y A LimMHattori M Correa andM P GuptaldquoA search for anti-viral properties in Panamanian medicinalplants the effects on HIV and its essential enzymesrdquo Journal ofEthnopharmacology vol 64 no 1 pp 15ndash22 1998
[63] M Hattori T Nakabayashi Y A Lim et al ldquoInhibitory effectsof various Ayurvedic and Panamanian medicinal plants onthe infection of herpes simplex virus-1 in vitro and in vivordquoPhytotherapy Research vol 9 no 4 pp 270ndash276 1995
[64] I Kola and J Landis ldquoCan the pharmaceutical industry reduceattrition ratesrdquoNature Reviews Drug Discovery vol 3 no 8 pp711ndash716 2004
[65] H Olson G Betton D Robinson et al ldquoConcordance ofthe toxicity of pharmaceuticals in humans and in animalsrdquoRegulatory Toxicology and Pharmacology vol 32 no 1 pp 56ndash67 2000
Evidence-Based Complementary and Alternative Medicine 7
Table 7 Reported IC50 values (120583gmL) of selected P bleo phytoconstituents on human cell lines [28]
Compound IC50 (120583gmL) of different cell linesKB MCF7 CasKi HCT 116 A549 MRC-5
Dihydroactinidiolide 67 30 40 5 97 913120573-sitosterol gt100 72 62 gt100 78 gt10024-ditertbutylphenol 081 575 45 29 6 20120572-tocopherol 8 75 6 31 6 305Phytol 71 34 18 100 31 741Mixture of sterols gt100 gt100 gt100 gt100 gt100 gt100Doxorubicin 13 times 10minus2 76 times 10minus2 60 times 10minus3 36 times 10minus1 22 times 10minus1 55 times 10minus1
A549 human lung carcinoma cell line CasKi human cervical carcinoma cell Line HCT116 human colon carcinoma cell Line KB human nasopharyngealepidermoid carcinoma cell Line MCF-7 hormone dependent breast carcinoma cell Line MRC-5 normal human fibroblast cell Lines
Gupta et al [22] reported high tumor inhibition activityin ldquopotato disc inhibition assayrdquo using crown gall tumors(LC5077 ppm)Their result was accompanied by a significant
DNA peak reduction in the DNA intercalation test for themethanol extract of the whole plant
To date no report is available on the in vivo antiprolifer-ative activities of P bleo
(1) Cytotoxic Components Some of the cytotoxic componentsin P bleo have been reported Table 7 shows the reported IC
50
(120583gmL) values of these components in the different humancell lines The effects of these compounds and the mixture ofthe isolated sterols were not as high as doxorubicin that isa chemotherapy drug [28] In another study phytol isolatedfrom P bleo leaves was found to have a significant antitumoractivity against some mouse cancer cell lines [36]
(2) Proposed Antiproliferative Mechanism The antiprolifera-tive activity of the methanol extract of P bleo against humanbreast carcinoma cell line (T-47D) was found to be apoptoticin nature through the activation of caspase-3 and c-mycpathways [40] Caspase-3 and c-myc are frequently activateddeath proteases which catalyze the specific cleavage of manykey cellular proteins They are also essential for normaldevelopment of the tissues as well as apoptosis in the tissuesand cell types [53] Komiya et al [54] reported the inductionof apoptosis as a mechanism of action for cytotoxic activityof phytol DNA intercalation is another proposedmechanismof antiproliferative activity for P bleo [22] However in somestudies P bleo did not show appreciable cytotoxic effect [32]Differences in the sources of plants extractionmethods assaymethods and cell lines can be the possible reasons for thesediscrepancies On the other hand P bleo may contain someprodrugs which are metabolized to the active metabolitesTherefore further studies are needed to better understand itsantiproliferative activity
Apart from the cytotoxic activities against cancer celllines crudemethanol extract and its fractions (hexane waterand ethyl acetate) did not show any cytotoxicity to the normalhuman fibroblast cell lines MRC-5 [36]
342 Antioxidant Activity The adverse effects of oxida-tive stress on human health have become a serious issueOxidative stress causes production of free radicals in thebody that facilitate the development of degenerative diseasessuch as cardiovascular diseases cancers neurodegenerativedisorders [55] Alzheimerrsquos and inflammatory diseases [56]One solution to this problem is to supplement the diet withantioxidant compounds found in natural plant sources [57]Hence in the literature the antioxidant effects of P bleo wereevaluated using different assays as follows
22-Diphenyl-1-picrylhydrazyl Hydrate (DPPH) Assay Themethanol dichloromethane ethyl acetate and hexaneextracts of P bleo leaves were tested [8 25] The hexaneextract exhibited the most effective radical scavengingactivity (EC
50210 120583gmL) followed by the ethyl acetate
extract (EC50
225120583gmL) This spectrophotometric assayuses a stable radical 221015840-diphenylpicrylhydrazyl (DPPH) asa reagent [8 25]
Ferric Reducing Antioxidant Potential Assay (FRAP) Thehexane water and methanol extracts of P bleo leaves werefound to reduce Fe3+ferric cyanide complex to the ferrousform Although the reduction was statistically significant itwas not more than ascorbic acid (vitamin C) and butylatedhydroxyanisole (BHA) as positive controls [25] Hassanba-glou et al [37] compared the antioxidant activity of the ethylacetate extract with that of hexane ethanol and methanolextracts They showed that the ethyl acetate extract hadsignificantly higher antioxidant properties compared to therest of the tested extracts FRAP measures the ability of testsamples to reduce ferric ion to the ferrous form of TPTZ(246-tripyridyl-s-triazine)
120573-Carotene-Linoleic Bleaching AssayThe ethyl acetate extractof P bleo demonstrated the strongest antioxidant activityfollowed by the methanol extract reported by Sim et al [25]In this assay the linoleate free radicals formed during thereaction are neutralized by antioxidants
8 Evidence-Based Complementary and Alternative Medicine
Table8Re
ported
effectsof
Pbleo
extractson
theg
rowth
ofselected
bacteriaandfung
i
Organism
Antibacteria
land
antifun
galeffectof
thee
xtracts
Positivec
ontro
lRe
ferences
Methano
lWater
Hexane
Dichloroethane
Ethylacetate
Chloroform
Bacillussubtilisa
minusNA
minusminus
minusNA
Streptom
ycinlowast
[8]
minusminus
minusNA
minusNA
Gentamicinampicillin
[41]
NA
NA
minusminus
NA
NA
Streptom
ycin
[38]
Escherich
iacolib
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Escherich
iacolia
minusminus
minusNA
minusNA
Gentamicinampicillin
[41]
Helicobacterpylorib
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Klebsiella
pneumoniaeb
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Methicillin
resistant
Staphylococcus
aureus
aminus
NA
minus++
+minus
NA
Streptom
ycinlowast
[8]
NA
NA
minus++
NA
NA
Streptom
ycin
[38]
Mycobacteriu
msm
egmatisb
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Pseudomonas
aeruginosa
a++
NA
+++
++
NA
Streptom
ycin
[8]
+minus
minusNA
+NA
Gentamicinampicillin
[41]
NA
NA
+++
+NA
NA
Streptom
ycinlowast
[38]
Pseudomonas
aeruginosa
bminus
NA
NA
minusNA
NA
Streptom
ycin
[42]
Salm
onellacholeraesuisa
++NA
+++
minusminus
NA
Streptom
ycinlowast
[8]
NA
NA
+++
minusNA
NA
Streptom
ycin
[38]
Staphylococcus
aureus
bminus
NA
NA
minusNA
NA
Streptom
ycin
[42]
Staphylococcus
aureus
aminus
minusminus
NA
minusNA
Gentamicinampicillin
[41]
Cand
idaalbicans
cminus
minusNA
NA
NA
minusProp
icon
azolemicon
azole
[43]
Cand
idaalbicans
bminus
NA
NA
minusNA
NA
Amph
otericin
B[42]
Cladosporiu
mcucumerinum
c+
+NA
NA
NA
+Prop
icon
azolemicon
azole
[43]
a Thes
creening
fora
ntibacteria
leffectwas
carriedou
tbyd
eterminingthez
oneo
finh
ibition
usingpaperd
isc+
stand
sfor
activ
itybetween6ndash
9mm+
+sta
ndsfor
activ
itybetween9ndash
14mm+
++stands
fora
ctivity
morethan14mm
[38]
b (+)
stand
sfor
activ
ityat100120583
gmLforE
coliS
aureusK
pneum
oniaeMsmegmatis
CalbicanceP
aeruginosa
andat125120583gmLforH
pylori(minus)stand
sfor
inactiv
esam
ples
c agaro
verla
yassayand(+)stand
sfor
activ
eextractsa
t50120583
gmL(minus)stand
sfor
inactiv
eextract
NAnot
applicableas
thereisn
orepo
rtin
theliterature
lowastStreptom
ycin
show
ed20
to23
mm
inhibitio
nzoneTh
eresto
fthe
studies
didno
treportthe
exactvalue
oftheinh
ibition
fortheirpo
sitivec
ontro
ls
Evidence-Based Complementary and Alternative Medicine 9
In general although different studies used plant materialsfrom different sources and nonsimilar extraction methodsethyl acetate and hexane extracts appear to be the strongestantioxidant extracts from the P bleo leaves [8 25 37]Moreover this antioxidant capacity is strongly associatedwith the total phenolic compounds and flavonoid content ofthe plant leaves [25 37 58] The above studies suggest thatP bleo has antioxidant properties which can be one of thepossible reasons for its traditional usage for detoxificationand prevention of cancer
343 Antimicrobial Properties P bleo has been shown topossess antibacterial antiviral and antifungal properties invitro Table 8 shows the effect of P bleo extracts on selectedbacteria and fungi As can be seen the methanol andhexane extracts demonstrated great antibacterial activitiesagainst Salmonella choleraesuis and Pseudomonas aeruginosaIn addition its dichloromethane extract showed promisingantibacterial effect againstMethicillin resistant Staphylococcusaureus [8 38] All of the mentioned bacteria are amongthe main causes of nosocomial infections and they havebeen developing antibiotic resistance [59ndash61] Therefore thepotential antibacterial activity of P bleo needs to be furtherinvestigated to identify the lead(s) antibacterial compo-nent(s)
The antifungal activity of the water and methanol extractof P bleo leaves against Cladosporium cucumerinum a plantpathogenic fungus has been reported [43] but they were notactive against Candida albicans a common human pathogen[42 43]
The antiviral properties of the water and methanolextracts of P bleo leaves were evaluated against HerpesSimplex Virus-I (HSV-1) andHuman Immunodeficiency Virus(HIV) by Matsuse et al [62] Both of the extracts demon-strated anti-HIV activity However the result of this studywas not promising because of the low selectivity index of094 Besides in another study by Hattori et al [63] the sameextracts did not demonstrate any antiviral activity againstHSV-1 In general the available data on the antiviral activityof P bleo is neither sufficient nor conclusive Thereforefurther research needs to be carried out
344 Antiparasitic Properties The only antiparasitic inves-tigation on P bleo was reported by Marston et al [52] Intheir study the chloroform methanol and water extractsof this plant did not exert any antiparasitic activity againstschistosomiasis
345 Neutralizing Snake Venom Otero et al [33] evaluatedthe neutralizing effect of the ethanol extract of P bleo onhemorrhagic activity of ldquoBothrops atrox venomrdquo in miceThisextract did not show any neutralizing effect against the testedvenom
346 Antinociceptive Properties Wahab et al [35] evaluatedthe antinociceptive activity of the ethanol extract and itsfractions using two in vivo analgesic models peripheralformalin-induced licking and acetic acid-induced abdominal
writhing They showed that the ethanol extract hexanefraction dichloromethane fraction and ethyl acetate fractionof P bleo had moderate antinociceptive effects However nocompound was identified in their study
35 Toxicity Studies Acute toxicity effect of the leaversquosextracts of P bleo was evaluated by in vitro and in vivostudies Er et al [32] showed that the water extract may formmutagenic compound(s) upon metabolization by the liverenzymes in vitro In another study by Gupta et al [22] themethanol extract of the whole plant had moderate toxicity inbrine shrimp toxicity assay (LD
5077 ppm) In the only in vivo
study by Sim et al [31] the methanol extract did not have anytoxicity effect on ICR mice (LD
50gt 2500mgkg) Although
animalmodels have around 70ndash80 predictability for humantoxicities [64 65] the long term toxicity and themutagenicityof metabolites of P bleo should be further investigated
4 Conclusion
A comprehensive review on Pereskia bleo has been presentedIt provides an overview of the botanical characteristics tra-ditional usage phytoconstituents pharmacological activitiesand safety of P bleo The current review highlights theassociation between the traditional usage of the plant andthe reported anticancer antibacterial and antinociceptiveeffects tested in different studies Although P bleo has beentraditionally used for a variety of therapeutic and prophy-lactic purposes only a few of them has been investigatedHence more research is warranted to further study itsbiological activities and chemical properties to understandits traditional usage and to develop novel therapeuticsUnderstanding the traditional uses knowing the availablescientific evidences and identifying the gaps in research willallow the proper translation of promising research results intoa safe and efficacious usage of herbal medicine and discoveryof new therapeutics It will also assist in setting appropriatepolicy and guidelines in the usage of herbal medicine
Conflict of Interests
All authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgments
Funding from the National University of Singapore (NUS)research Grant (R-148-000-137-112 to KHL) and LeewardPacific Pte Ltd (R-148-000-140-592 to KHL) and researchscholarship from the Singapore International GraduateAward (SINGA SZ) are acknowledged
References
[1] C Wiart Medicinal Plants of Asia and the Pacific Drugs of theFuture World Scientific Singapore 2006
[2] N L Britton and J N Rose The Cactaceae Descriptions andIllustrations of Plants of the Cactus Family Dover PublicationsWashington DC USA 2009
10 Evidence-Based Complementary and Alternative Medicine
[3] E J Edwards and M J Donoghue ldquoPereskia and the origin ofthe cactus life-formrdquo American Naturalist vol 167 no 6 pp777ndash793 2006
[4] E J Edwards R Nyffeler and M J Donoghue ldquoBasal cactusphylogeny implications of Pereskia (Cactaceae) paraphyly forthe transition to the cactus life formrdquo American Journal ofBotany vol 92 no 7 pp 1177ndash1188 2005
[5] R M Ogburn and E J Edwards ldquoAnatomical variation in Cac-taceae and relatives trait lability and evolutionary innovationrdquoAmerican Journal of Botany vol 96 no 2 pp 391ndash408 2009
[6] CM Boo C LOu-Yang andKOmar-Hor 1001Garden Plantsin Singapore National Parks Board Singapore 2nd edition2007
[7] Singapore Npark Board NParks FloraampFouna web 2010httpsflorafaunawebnparksgovsgSpecial-Pagesplant-detailaspxid=2324
[8] S I A Wahab A B Abdul S M Mohan A S Al-Zubairi MM Elhassan andMY Ibrahim ldquoBiological activities ofPereskiableo extractsrdquo International Journal of Pharmacology vol 5 no1 pp 71ndash75 2009
[9] R T Barcenas C Yesson and J A Hawkins ldquoMolecular sys-tematics of the CactaceaerdquoCladistics vol 27 no 5 pp 470ndash4892011
[10] K Y Chong H T Tan and R T Corlett A Checklist of theTotal Vascular Plant Flora of Singapore Native Naturalised andCultivated Species Raffles Museum of Biodiversity ResearchNational University of Singapore Singapore 2009 httprmbrnusedusgraffles museum pubflora of singapore tcpdf
[11] A M Sri Nurestri K S Sim and A W Norhanom ldquoPhy-tochemical and cytotoxic investigations of Pereskia grandifoliaHaw (Cactaceae) leavesrdquo Journal of Biological Sciences vol 9no 5 pp 488ndash493 2009
[12] E Anderson The Cactus Family pp 566ndash568 Timber PressPuritana Ore USA 1st edition 2001
[13] R P Wunderlin and B F Hansen ldquoAtlas of Florida VascularPlantsrdquo 2008 httpwwwplantatlasusfedu
[14] N P Taylor D Zappi P Braun and M Machado ldquoPereskiaaculeata Iucn Red List of Threatened Species Version 2013 2rdquo2013 httpwwwiucnredlistorg
[15] E Pooley A Field Guide to Wild Flowers KwaZulu Natal and theEastern Region Natal Flora Publications Trust Durban SouthAfrica 1999
[16] A G I Natural Heritage Trust ldquoWeedManagementGuide Leafcactus Pereskia aculeatardquo 2003 httpwwwenvironmentgovaubiodiversityinvasiveweedspublicationsguidelinesalertpubsp-aculeatapdf
[18] B E Leuenberger ldquoPereskia Maihuenia and Blossfeldia-taxonomic history updates and notesrdquo Haseltonia no 14 pp54ndash93 2008
[19] J Nugent ldquoPermaculture Plants agaves and cactirdquo 2007 httpbooksgooglecomsgbooksid=YVwMM2OdO34Campq=Pereskia+bleov=snippetampq=Pereskia20bleoampf=false
[20] B E Leuenberger ldquoHumboldt amp Bonplandrsquos Cactaceae in theherbaria at Paris and Berlinrdquo Willdenowia vol 32 pp 137ndash1532002
[21] KA LiamasTropical Flowering Plants AGuide to Identificationand Cultivation Timber Press Portland Ore USA 2003
[22] M P Gupta A Monge G A Karikas et al ldquoScreening of Pana-manian medicinal plants for brine shrimp toxicity crown
gall tumor inhibition cytotoxicity and DNA intercalationrdquoPharmaceutical Biology vol 34 no 1 pp 19ndash27 1996
[23] C C Kazama D T Uchida K N Canzi et al ldquoInvolvementof arginine-vasopressin in the diuretic and hypotensive effectsof Pereskia grandifoliaHaw (Cactaceae)rdquo Journal of Ethnophar-macology vol 144 no 1 pp 86ndash93 2012
[25] K S Sim A M Sri Nurestri and A W Norhanom ldquoPhenoliccontent and antioxidant activity of crude and fractionatedextracts of Pereskia bleo (Kunth) DC (Cactaceae)rdquo AfricanJournal of Pharmacy and Pharmacology vol 4 no 5 pp 193ndash201 2010
[26] EMurillo A JMelendez-Martınez and F Portugal ldquoScreeningof vegetables and fruits from Panama for rich sources of luteinand zeaxanthinrdquo Food Chemistry vol 122 no 1 pp 167ndash1722010
[27] K Hostettmann A Marston M Maillard and M HamburgerPhytochemistry of Plants Used in Traditional Medicine pp 373ndash376 Oxford University Press Oxford UK 1995
[28] S N A Malek S K Shin N A Wahab and H Yaacob ldquoCyto-toxic components of Pereskia bleo (Kunth) DC (Cactaceae)leavesrdquoMolecules vol 14 no 5 pp 1713ndash1724 2009
[29] M P Gupta A Correa DMireya et al ldquoMedicinal plant inven-tory of Kuna Indians part 1rdquo Journal of Ethnopharmacology vol40 no 2 pp 77ndash109 1993
[30] A Rahmat F P Saib and N A Buslima ldquoComparing theeffect of ficus benjamina extract and Pereskia saecnarosa extracton tthe level of micro and macro minerals in normal andinduced liver cancer ratsrdquo in Proceedings of the 4th InternationalConference on Biomedical Engineering in Vietnam pp 208ndash2121980
[31] K S Sim A M Sri Nurestri S K Sinniah K H Kim and AW Norhanom ldquoAcute oral toxicity of Pereskia bleo and Pereskiagrandifolia inmicerdquo PharmacognosyMagazine vol 6 no 21 pp67ndash70 2010
[32] H M Er E Cheng and A K Radhakrishnan ldquoAnti-proliferative and mutagenic activities of aqueous and methanolextracts of leaves from Pereskia bleo (Kunth) DC (Cactaceae)rdquoJournal of Ethnopharmacology vol 113 no 3 pp 448ndash456 2007
[33] R Otero V Nunez J Barona et al ldquoSnakebites and ethnob-otany in the northwest region of Colombia part III neutral-ization of the haemorrhagic effect of Bothrops atrox venomrdquoJournal of Ethnopharmacology vol 73 no 1-2 pp 233ndash2412000
[34] P W Doetsch J M Cassady and J L McLaughlin ldquoCac-tus alkaloids XL Identification of mescaline and other 120573-phenethylamines in Pereskia Pereskiopsis and Islaya by use offluorescamine conjugatesrdquo Journal of Chromatography A vol189 no 1 pp 79ndash85 1980
[35] I R A Wahab C C Guilhon P D Fernandes and F BoylanldquoAnti-nociceptive activity of Pereskia bleo Kunth (Cactaceae)leaves extractsrdquo Journal of Ethnopharmacology vol 144 no 3pp 741ndash746 2012
[36] S N AMalek N AWahabH Yaacob et al ldquoCytotoxic activityof Pereskia bleo (Cactaceae) against selected human cell linesrdquoInternational Journal of Cancer Research vol 4 no 1 pp 20ndash272008
Evidence-Based Complementary and Alternative Medicine 11
[37] B Hassanbaglou A A Hamid A Roheeyati et al ldquoAntioxidantactivity of different extracts from leaves of Pereskia bleo (Cac-taceae)rdquo Journal of Meidinal Plants Research vol 6 no 15 pp2932ndash2937 2012
[38] S I Abbdewahab N M Ain A B Abdul M M E Tahaand T A T Ibrahim ldquoEnergy-dispersive X-raymicroanalysis ofelementsrsquo content and antimicrobial properties of Pereskia bleoandGoniothalamus umbrosusrdquoAfrican Journal of Biotechnologyvol 8 no 10 pp 2375ndash2378 2009
[39] S Y Liew E J Stanbridge K Yusoff and N ShafeeldquoHypoxia affects cellular responses to plant extractsrdquo Journal ofEthnopharmacology vol 144 no 2 pp 453ndash456 2012
[40] M L Tan S F Sulaiman N Najimuddin M R Samian and TS T Muhammad ldquoMethanolic extract of Pereskia bleo (Kunth)DC (Cactaceae) induces apoptosis in breast carcinoma T47-D cell linerdquo Journal of Ethnopharmacology vol 96 no 1-2 pp287ndash294 2005
[41] K Philip S N A Malek W Sani et al ldquoAntimicrobial activityof some medicinal plants from Malaysiardquo American Journal ofApplied Sciences vol 6 no 8 pp 1613ndash1617 2009
[42] T Ruegg A I Calderon E F Queiroz et al ldquo3-farnesyl-2-hydroxybenzoic acid is a new anti-Helicobacter pylori com-pound from Piper multiplinerviumrdquo Journal of Ethnopharma-cology vol 103 no 3 pp 461ndash467 2006
[43] L Rahalison M Hamburger K Hostettmann et al ldquoScreeningfor antifungal activity of Panamanian plantsrdquo InternationalJournal of Pharmacognosy vol 31 no 1 pp 68ndash76 1993
[44] A P D Candolle ldquoPereskia bleo (Kunth) DCrdquo 2011 httpwwwtropicosorgName5100482
[47] M Gardener ldquoTropical plants library onlinerdquo 2014 httpmgonlinecomarticlesexoticsaspx
[48] S Kurt ldquoStem of P grandifoliardquo 2014 httpwwwbiolibde[49] NRCS ldquoNatural Resources and Conservation Service of
USDA Plant profile of P grandifolia Hawrdquo 2013 httpplantsusdagovcoreprofilesymbol=PEGR14
[50] D C Sanders A S Grayson andT JMonaco ldquoMineral contentof tomato (Lycopersicon esculentum) and four competing weedspeciesrdquoWeed Science vol 29 no 5 pp 590ndash593 1981
[51] J M Geleijnse J C Witteman A A Bak J H den Breeijenand D E Grobbee ldquoReduction in blood pressure with a lowsodium high potassium high magnesium salt in older subjectswith mild to moderate hypertensionrdquo British Medical Journalvol 309 no 6952 pp 436ndash440 1994
[52] A Marston G Dudan M P Gupta P N Solis M D Correaand K Hostettmann ldquoScreening of Panamanian plants formolluscicidal activityrdquo Pharmaceutical Biology vol 34 no 1 pp15ndash18 1996
[53] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999
[54] T Komiya M Kyohkon S Ohwaki et al ldquoPhytol inducesprogrammed cell death in human lymphoid leukemia Molt 4Bcellsrdquo International Journal of Molecular Medicine vol 4 no 4pp 377ndash380 1999
[55] M Gerber M C Boutron-Ruault S Hercberg E Riboli AScalbert and M H Siess ldquoFood and cancer state of the art
about the protective effect of fruits and vegetablesrdquo Bulletin duCancer vol 89 no 3 pp 293ndash312 2002
[56] V di Matteo and E Esposito ldquoBiochemical and therapeuticeffects of antioxidants in the treatment of Alzheimerrsquos diseaseParkinsonrsquos disease and amyotrophic lateral sclerosisrdquo CurrentDrug Targets-CNSampNeurological Disorders vol 2 no 2 pp 95ndash107 2003
[57] P Knekt R Jarvinen A Reunanen and J Maatela ldquoFlavonoidintake and coronary mortality in Finland a cohort studyrdquoBritish Medical Journal vol 312 no 7029 pp 478ndash481 1996
[58] R A Mustafa A Abdul Hamid S Mohamed and F A BakarldquoTotal phenolic compounds flavonoids and radical scavengingactivity of 21 selected tropical plantsrdquo Journal of Food Sciencevol 75 no 1 pp C28ndashC35 2010
[59] E B Breidenstein C de la Fuente-Nunez and R E HancockldquoPseudomonas aeruginosa all roads lead to resistancerdquo Trendsin Microbiology vol 19 no 8 pp 419ndash426 2011
[60] C Chu C-H ChiuW-YWu C-H Chu T-P Liu and J T OuldquoLarge drug resistance virulence plasmids of clinical isolates ofSalmonella enterica serovar Choleraesuisrdquo Antimicrobial Agentsand Chemotherapy vol 45 no 8 pp 2299ndash2303 2001
[61] K Hiramatsu H Hanaki T Ino K Yabuta T Oguri andF Tenover ldquoMethicillin-resistant Staphylococcus aureus clini-cal strain with reduced vancomycin susceptibilityrdquo Journal ofAntimicrobial Chemotherapy vol 40 no 1 pp 135ndash136 1997
[62] I TMatsuse Y A LimMHattori M Correa andM P GuptaldquoA search for anti-viral properties in Panamanian medicinalplants the effects on HIV and its essential enzymesrdquo Journal ofEthnopharmacology vol 64 no 1 pp 15ndash22 1998
[63] M Hattori T Nakabayashi Y A Lim et al ldquoInhibitory effectsof various Ayurvedic and Panamanian medicinal plants onthe infection of herpes simplex virus-1 in vitro and in vivordquoPhytotherapy Research vol 9 no 4 pp 270ndash276 1995
[64] I Kola and J Landis ldquoCan the pharmaceutical industry reduceattrition ratesrdquoNature Reviews Drug Discovery vol 3 no 8 pp711ndash716 2004
[65] H Olson G Betton D Robinson et al ldquoConcordance ofthe toxicity of pharmaceuticals in humans and in animalsrdquoRegulatory Toxicology and Pharmacology vol 32 no 1 pp 56ndash67 2000
8 Evidence-Based Complementary and Alternative Medicine
Table8Re
ported
effectsof
Pbleo
extractson
theg
rowth
ofselected
bacteriaandfung
i
Organism
Antibacteria
land
antifun
galeffectof
thee
xtracts
Positivec
ontro
lRe
ferences
Methano
lWater
Hexane
Dichloroethane
Ethylacetate
Chloroform
Bacillussubtilisa
minusNA
minusminus
minusNA
Streptom
ycinlowast
[8]
minusminus
minusNA
minusNA
Gentamicinampicillin
[41]
NA
NA
minusminus
NA
NA
Streptom
ycin
[38]
Escherich
iacolib
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Escherich
iacolia
minusminus
minusNA
minusNA
Gentamicinampicillin
[41]
Helicobacterpylorib
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Klebsiella
pneumoniaeb
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Methicillin
resistant
Staphylococcus
aureus
aminus
NA
minus++
+minus
NA
Streptom
ycinlowast
[8]
NA
NA
minus++
NA
NA
Streptom
ycin
[38]
Mycobacteriu
msm
egmatisb
minusNA
NA
minusNA
NA
Streptom
ycin
[42]
Pseudomonas
aeruginosa
a++
NA
+++
++
NA
Streptom
ycin
[8]
+minus
minusNA
+NA
Gentamicinampicillin
[41]
NA
NA
+++
+NA
NA
Streptom
ycinlowast
[38]
Pseudomonas
aeruginosa
bminus
NA
NA
minusNA
NA
Streptom
ycin
[42]
Salm
onellacholeraesuisa
++NA
+++
minusminus
NA
Streptom
ycinlowast
[8]
NA
NA
+++
minusNA
NA
Streptom
ycin
[38]
Staphylococcus
aureus
bminus
NA
NA
minusNA
NA
Streptom
ycin
[42]
Staphylococcus
aureus
aminus
minusminus
NA
minusNA
Gentamicinampicillin
[41]
Cand
idaalbicans
cminus
minusNA
NA
NA
minusProp
icon
azolemicon
azole
[43]
Cand
idaalbicans
bminus
NA
NA
minusNA
NA
Amph
otericin
B[42]
Cladosporiu
mcucumerinum
c+
+NA
NA
NA
+Prop
icon
azolemicon
azole
[43]
a Thes
creening
fora
ntibacteria
leffectwas
carriedou
tbyd
eterminingthez
oneo
finh
ibition
usingpaperd
isc+
stand
sfor
activ
itybetween6ndash
9mm+
+sta
ndsfor
activ
itybetween9ndash
14mm+
++stands
fora
ctivity
morethan14mm
[38]
b (+)
stand
sfor
activ
ityat100120583
gmLforE
coliS
aureusK
pneum
oniaeMsmegmatis
CalbicanceP
aeruginosa
andat125120583gmLforH
pylori(minus)stand
sfor
inactiv
esam
ples
c agaro
verla
yassayand(+)stand
sfor
activ
eextractsa
t50120583
gmL(minus)stand
sfor
inactiv
eextract
NAnot
applicableas
thereisn
orepo
rtin
theliterature
lowastStreptom
ycin
show
ed20
to23
mm
inhibitio
nzoneTh
eresto
fthe
studies
didno
treportthe
exactvalue
oftheinh
ibition
fortheirpo
sitivec
ontro
ls
Evidence-Based Complementary and Alternative Medicine 9
In general although different studies used plant materialsfrom different sources and nonsimilar extraction methodsethyl acetate and hexane extracts appear to be the strongestantioxidant extracts from the P bleo leaves [8 25 37]Moreover this antioxidant capacity is strongly associatedwith the total phenolic compounds and flavonoid content ofthe plant leaves [25 37 58] The above studies suggest thatP bleo has antioxidant properties which can be one of thepossible reasons for its traditional usage for detoxificationand prevention of cancer
343 Antimicrobial Properties P bleo has been shown topossess antibacterial antiviral and antifungal properties invitro Table 8 shows the effect of P bleo extracts on selectedbacteria and fungi As can be seen the methanol andhexane extracts demonstrated great antibacterial activitiesagainst Salmonella choleraesuis and Pseudomonas aeruginosaIn addition its dichloromethane extract showed promisingantibacterial effect againstMethicillin resistant Staphylococcusaureus [8 38] All of the mentioned bacteria are amongthe main causes of nosocomial infections and they havebeen developing antibiotic resistance [59ndash61] Therefore thepotential antibacterial activity of P bleo needs to be furtherinvestigated to identify the lead(s) antibacterial compo-nent(s)
The antifungal activity of the water and methanol extractof P bleo leaves against Cladosporium cucumerinum a plantpathogenic fungus has been reported [43] but they were notactive against Candida albicans a common human pathogen[42 43]
The antiviral properties of the water and methanolextracts of P bleo leaves were evaluated against HerpesSimplex Virus-I (HSV-1) andHuman Immunodeficiency Virus(HIV) by Matsuse et al [62] Both of the extracts demon-strated anti-HIV activity However the result of this studywas not promising because of the low selectivity index of094 Besides in another study by Hattori et al [63] the sameextracts did not demonstrate any antiviral activity againstHSV-1 In general the available data on the antiviral activityof P bleo is neither sufficient nor conclusive Thereforefurther research needs to be carried out
344 Antiparasitic Properties The only antiparasitic inves-tigation on P bleo was reported by Marston et al [52] Intheir study the chloroform methanol and water extractsof this plant did not exert any antiparasitic activity againstschistosomiasis
345 Neutralizing Snake Venom Otero et al [33] evaluatedthe neutralizing effect of the ethanol extract of P bleo onhemorrhagic activity of ldquoBothrops atrox venomrdquo in miceThisextract did not show any neutralizing effect against the testedvenom
346 Antinociceptive Properties Wahab et al [35] evaluatedthe antinociceptive activity of the ethanol extract and itsfractions using two in vivo analgesic models peripheralformalin-induced licking and acetic acid-induced abdominal
writhing They showed that the ethanol extract hexanefraction dichloromethane fraction and ethyl acetate fractionof P bleo had moderate antinociceptive effects However nocompound was identified in their study
35 Toxicity Studies Acute toxicity effect of the leaversquosextracts of P bleo was evaluated by in vitro and in vivostudies Er et al [32] showed that the water extract may formmutagenic compound(s) upon metabolization by the liverenzymes in vitro In another study by Gupta et al [22] themethanol extract of the whole plant had moderate toxicity inbrine shrimp toxicity assay (LD
5077 ppm) In the only in vivo
study by Sim et al [31] the methanol extract did not have anytoxicity effect on ICR mice (LD
50gt 2500mgkg) Although
animalmodels have around 70ndash80 predictability for humantoxicities [64 65] the long term toxicity and themutagenicityof metabolites of P bleo should be further investigated
4 Conclusion
A comprehensive review on Pereskia bleo has been presentedIt provides an overview of the botanical characteristics tra-ditional usage phytoconstituents pharmacological activitiesand safety of P bleo The current review highlights theassociation between the traditional usage of the plant andthe reported anticancer antibacterial and antinociceptiveeffects tested in different studies Although P bleo has beentraditionally used for a variety of therapeutic and prophy-lactic purposes only a few of them has been investigatedHence more research is warranted to further study itsbiological activities and chemical properties to understandits traditional usage and to develop novel therapeuticsUnderstanding the traditional uses knowing the availablescientific evidences and identifying the gaps in research willallow the proper translation of promising research results intoa safe and efficacious usage of herbal medicine and discoveryof new therapeutics It will also assist in setting appropriatepolicy and guidelines in the usage of herbal medicine
Conflict of Interests
All authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgments
Funding from the National University of Singapore (NUS)research Grant (R-148-000-137-112 to KHL) and LeewardPacific Pte Ltd (R-148-000-140-592 to KHL) and researchscholarship from the Singapore International GraduateAward (SINGA SZ) are acknowledged
References
[1] C Wiart Medicinal Plants of Asia and the Pacific Drugs of theFuture World Scientific Singapore 2006
[2] N L Britton and J N Rose The Cactaceae Descriptions andIllustrations of Plants of the Cactus Family Dover PublicationsWashington DC USA 2009
10 Evidence-Based Complementary and Alternative Medicine
[3] E J Edwards and M J Donoghue ldquoPereskia and the origin ofthe cactus life-formrdquo American Naturalist vol 167 no 6 pp777ndash793 2006
[4] E J Edwards R Nyffeler and M J Donoghue ldquoBasal cactusphylogeny implications of Pereskia (Cactaceae) paraphyly forthe transition to the cactus life formrdquo American Journal ofBotany vol 92 no 7 pp 1177ndash1188 2005
[5] R M Ogburn and E J Edwards ldquoAnatomical variation in Cac-taceae and relatives trait lability and evolutionary innovationrdquoAmerican Journal of Botany vol 96 no 2 pp 391ndash408 2009
[6] CM Boo C LOu-Yang andKOmar-Hor 1001Garden Plantsin Singapore National Parks Board Singapore 2nd edition2007
[7] Singapore Npark Board NParks FloraampFouna web 2010httpsflorafaunawebnparksgovsgSpecial-Pagesplant-detailaspxid=2324
[8] S I A Wahab A B Abdul S M Mohan A S Al-Zubairi MM Elhassan andMY Ibrahim ldquoBiological activities ofPereskiableo extractsrdquo International Journal of Pharmacology vol 5 no1 pp 71ndash75 2009
[9] R T Barcenas C Yesson and J A Hawkins ldquoMolecular sys-tematics of the CactaceaerdquoCladistics vol 27 no 5 pp 470ndash4892011
[10] K Y Chong H T Tan and R T Corlett A Checklist of theTotal Vascular Plant Flora of Singapore Native Naturalised andCultivated Species Raffles Museum of Biodiversity ResearchNational University of Singapore Singapore 2009 httprmbrnusedusgraffles museum pubflora of singapore tcpdf
[11] A M Sri Nurestri K S Sim and A W Norhanom ldquoPhy-tochemical and cytotoxic investigations of Pereskia grandifoliaHaw (Cactaceae) leavesrdquo Journal of Biological Sciences vol 9no 5 pp 488ndash493 2009
[12] E Anderson The Cactus Family pp 566ndash568 Timber PressPuritana Ore USA 1st edition 2001
[13] R P Wunderlin and B F Hansen ldquoAtlas of Florida VascularPlantsrdquo 2008 httpwwwplantatlasusfedu
[14] N P Taylor D Zappi P Braun and M Machado ldquoPereskiaaculeata Iucn Red List of Threatened Species Version 2013 2rdquo2013 httpwwwiucnredlistorg
[15] E Pooley A Field Guide to Wild Flowers KwaZulu Natal and theEastern Region Natal Flora Publications Trust Durban SouthAfrica 1999
[16] A G I Natural Heritage Trust ldquoWeedManagementGuide Leafcactus Pereskia aculeatardquo 2003 httpwwwenvironmentgovaubiodiversityinvasiveweedspublicationsguidelinesalertpubsp-aculeatapdf
[18] B E Leuenberger ldquoPereskia Maihuenia and Blossfeldia-taxonomic history updates and notesrdquo Haseltonia no 14 pp54ndash93 2008
[19] J Nugent ldquoPermaculture Plants agaves and cactirdquo 2007 httpbooksgooglecomsgbooksid=YVwMM2OdO34Campq=Pereskia+bleov=snippetampq=Pereskia20bleoampf=false
[20] B E Leuenberger ldquoHumboldt amp Bonplandrsquos Cactaceae in theherbaria at Paris and Berlinrdquo Willdenowia vol 32 pp 137ndash1532002
[21] KA LiamasTropical Flowering Plants AGuide to Identificationand Cultivation Timber Press Portland Ore USA 2003
[22] M P Gupta A Monge G A Karikas et al ldquoScreening of Pana-manian medicinal plants for brine shrimp toxicity crown
gall tumor inhibition cytotoxicity and DNA intercalationrdquoPharmaceutical Biology vol 34 no 1 pp 19ndash27 1996
[23] C C Kazama D T Uchida K N Canzi et al ldquoInvolvementof arginine-vasopressin in the diuretic and hypotensive effectsof Pereskia grandifoliaHaw (Cactaceae)rdquo Journal of Ethnophar-macology vol 144 no 1 pp 86ndash93 2012
[25] K S Sim A M Sri Nurestri and A W Norhanom ldquoPhenoliccontent and antioxidant activity of crude and fractionatedextracts of Pereskia bleo (Kunth) DC (Cactaceae)rdquo AfricanJournal of Pharmacy and Pharmacology vol 4 no 5 pp 193ndash201 2010
[26] EMurillo A JMelendez-Martınez and F Portugal ldquoScreeningof vegetables and fruits from Panama for rich sources of luteinand zeaxanthinrdquo Food Chemistry vol 122 no 1 pp 167ndash1722010
[27] K Hostettmann A Marston M Maillard and M HamburgerPhytochemistry of Plants Used in Traditional Medicine pp 373ndash376 Oxford University Press Oxford UK 1995
[28] S N A Malek S K Shin N A Wahab and H Yaacob ldquoCyto-toxic components of Pereskia bleo (Kunth) DC (Cactaceae)leavesrdquoMolecules vol 14 no 5 pp 1713ndash1724 2009
[29] M P Gupta A Correa DMireya et al ldquoMedicinal plant inven-tory of Kuna Indians part 1rdquo Journal of Ethnopharmacology vol40 no 2 pp 77ndash109 1993
[30] A Rahmat F P Saib and N A Buslima ldquoComparing theeffect of ficus benjamina extract and Pereskia saecnarosa extracton tthe level of micro and macro minerals in normal andinduced liver cancer ratsrdquo in Proceedings of the 4th InternationalConference on Biomedical Engineering in Vietnam pp 208ndash2121980
[31] K S Sim A M Sri Nurestri S K Sinniah K H Kim and AW Norhanom ldquoAcute oral toxicity of Pereskia bleo and Pereskiagrandifolia inmicerdquo PharmacognosyMagazine vol 6 no 21 pp67ndash70 2010
[32] H M Er E Cheng and A K Radhakrishnan ldquoAnti-proliferative and mutagenic activities of aqueous and methanolextracts of leaves from Pereskia bleo (Kunth) DC (Cactaceae)rdquoJournal of Ethnopharmacology vol 113 no 3 pp 448ndash456 2007
[33] R Otero V Nunez J Barona et al ldquoSnakebites and ethnob-otany in the northwest region of Colombia part III neutral-ization of the haemorrhagic effect of Bothrops atrox venomrdquoJournal of Ethnopharmacology vol 73 no 1-2 pp 233ndash2412000
[34] P W Doetsch J M Cassady and J L McLaughlin ldquoCac-tus alkaloids XL Identification of mescaline and other 120573-phenethylamines in Pereskia Pereskiopsis and Islaya by use offluorescamine conjugatesrdquo Journal of Chromatography A vol189 no 1 pp 79ndash85 1980
[35] I R A Wahab C C Guilhon P D Fernandes and F BoylanldquoAnti-nociceptive activity of Pereskia bleo Kunth (Cactaceae)leaves extractsrdquo Journal of Ethnopharmacology vol 144 no 3pp 741ndash746 2012
[36] S N AMalek N AWahabH Yaacob et al ldquoCytotoxic activityof Pereskia bleo (Cactaceae) against selected human cell linesrdquoInternational Journal of Cancer Research vol 4 no 1 pp 20ndash272008
Evidence-Based Complementary and Alternative Medicine 11
[37] B Hassanbaglou A A Hamid A Roheeyati et al ldquoAntioxidantactivity of different extracts from leaves of Pereskia bleo (Cac-taceae)rdquo Journal of Meidinal Plants Research vol 6 no 15 pp2932ndash2937 2012
[38] S I Abbdewahab N M Ain A B Abdul M M E Tahaand T A T Ibrahim ldquoEnergy-dispersive X-raymicroanalysis ofelementsrsquo content and antimicrobial properties of Pereskia bleoandGoniothalamus umbrosusrdquoAfrican Journal of Biotechnologyvol 8 no 10 pp 2375ndash2378 2009
[39] S Y Liew E J Stanbridge K Yusoff and N ShafeeldquoHypoxia affects cellular responses to plant extractsrdquo Journal ofEthnopharmacology vol 144 no 2 pp 453ndash456 2012
[40] M L Tan S F Sulaiman N Najimuddin M R Samian and TS T Muhammad ldquoMethanolic extract of Pereskia bleo (Kunth)DC (Cactaceae) induces apoptosis in breast carcinoma T47-D cell linerdquo Journal of Ethnopharmacology vol 96 no 1-2 pp287ndash294 2005
[41] K Philip S N A Malek W Sani et al ldquoAntimicrobial activityof some medicinal plants from Malaysiardquo American Journal ofApplied Sciences vol 6 no 8 pp 1613ndash1617 2009
[42] T Ruegg A I Calderon E F Queiroz et al ldquo3-farnesyl-2-hydroxybenzoic acid is a new anti-Helicobacter pylori com-pound from Piper multiplinerviumrdquo Journal of Ethnopharma-cology vol 103 no 3 pp 461ndash467 2006
[43] L Rahalison M Hamburger K Hostettmann et al ldquoScreeningfor antifungal activity of Panamanian plantsrdquo InternationalJournal of Pharmacognosy vol 31 no 1 pp 68ndash76 1993
[44] A P D Candolle ldquoPereskia bleo (Kunth) DCrdquo 2011 httpwwwtropicosorgName5100482
[47] M Gardener ldquoTropical plants library onlinerdquo 2014 httpmgonlinecomarticlesexoticsaspx
[48] S Kurt ldquoStem of P grandifoliardquo 2014 httpwwwbiolibde[49] NRCS ldquoNatural Resources and Conservation Service of
USDA Plant profile of P grandifolia Hawrdquo 2013 httpplantsusdagovcoreprofilesymbol=PEGR14
[50] D C Sanders A S Grayson andT JMonaco ldquoMineral contentof tomato (Lycopersicon esculentum) and four competing weedspeciesrdquoWeed Science vol 29 no 5 pp 590ndash593 1981
[51] J M Geleijnse J C Witteman A A Bak J H den Breeijenand D E Grobbee ldquoReduction in blood pressure with a lowsodium high potassium high magnesium salt in older subjectswith mild to moderate hypertensionrdquo British Medical Journalvol 309 no 6952 pp 436ndash440 1994
[52] A Marston G Dudan M P Gupta P N Solis M D Correaand K Hostettmann ldquoScreening of Panamanian plants formolluscicidal activityrdquo Pharmaceutical Biology vol 34 no 1 pp15ndash18 1996
[53] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999
[54] T Komiya M Kyohkon S Ohwaki et al ldquoPhytol inducesprogrammed cell death in human lymphoid leukemia Molt 4Bcellsrdquo International Journal of Molecular Medicine vol 4 no 4pp 377ndash380 1999
[55] M Gerber M C Boutron-Ruault S Hercberg E Riboli AScalbert and M H Siess ldquoFood and cancer state of the art
about the protective effect of fruits and vegetablesrdquo Bulletin duCancer vol 89 no 3 pp 293ndash312 2002
[56] V di Matteo and E Esposito ldquoBiochemical and therapeuticeffects of antioxidants in the treatment of Alzheimerrsquos diseaseParkinsonrsquos disease and amyotrophic lateral sclerosisrdquo CurrentDrug Targets-CNSampNeurological Disorders vol 2 no 2 pp 95ndash107 2003
[57] P Knekt R Jarvinen A Reunanen and J Maatela ldquoFlavonoidintake and coronary mortality in Finland a cohort studyrdquoBritish Medical Journal vol 312 no 7029 pp 478ndash481 1996
[58] R A Mustafa A Abdul Hamid S Mohamed and F A BakarldquoTotal phenolic compounds flavonoids and radical scavengingactivity of 21 selected tropical plantsrdquo Journal of Food Sciencevol 75 no 1 pp C28ndashC35 2010
[59] E B Breidenstein C de la Fuente-Nunez and R E HancockldquoPseudomonas aeruginosa all roads lead to resistancerdquo Trendsin Microbiology vol 19 no 8 pp 419ndash426 2011
[60] C Chu C-H ChiuW-YWu C-H Chu T-P Liu and J T OuldquoLarge drug resistance virulence plasmids of clinical isolates ofSalmonella enterica serovar Choleraesuisrdquo Antimicrobial Agentsand Chemotherapy vol 45 no 8 pp 2299ndash2303 2001
[61] K Hiramatsu H Hanaki T Ino K Yabuta T Oguri andF Tenover ldquoMethicillin-resistant Staphylococcus aureus clini-cal strain with reduced vancomycin susceptibilityrdquo Journal ofAntimicrobial Chemotherapy vol 40 no 1 pp 135ndash136 1997
[62] I TMatsuse Y A LimMHattori M Correa andM P GuptaldquoA search for anti-viral properties in Panamanian medicinalplants the effects on HIV and its essential enzymesrdquo Journal ofEthnopharmacology vol 64 no 1 pp 15ndash22 1998
[63] M Hattori T Nakabayashi Y A Lim et al ldquoInhibitory effectsof various Ayurvedic and Panamanian medicinal plants onthe infection of herpes simplex virus-1 in vitro and in vivordquoPhytotherapy Research vol 9 no 4 pp 270ndash276 1995
[64] I Kola and J Landis ldquoCan the pharmaceutical industry reduceattrition ratesrdquoNature Reviews Drug Discovery vol 3 no 8 pp711ndash716 2004
[65] H Olson G Betton D Robinson et al ldquoConcordance ofthe toxicity of pharmaceuticals in humans and in animalsrdquoRegulatory Toxicology and Pharmacology vol 32 no 1 pp 56ndash67 2000
Evidence-Based Complementary and Alternative Medicine 9
In general although different studies used plant materialsfrom different sources and nonsimilar extraction methodsethyl acetate and hexane extracts appear to be the strongestantioxidant extracts from the P bleo leaves [8 25 37]Moreover this antioxidant capacity is strongly associatedwith the total phenolic compounds and flavonoid content ofthe plant leaves [25 37 58] The above studies suggest thatP bleo has antioxidant properties which can be one of thepossible reasons for its traditional usage for detoxificationand prevention of cancer
343 Antimicrobial Properties P bleo has been shown topossess antibacterial antiviral and antifungal properties invitro Table 8 shows the effect of P bleo extracts on selectedbacteria and fungi As can be seen the methanol andhexane extracts demonstrated great antibacterial activitiesagainst Salmonella choleraesuis and Pseudomonas aeruginosaIn addition its dichloromethane extract showed promisingantibacterial effect againstMethicillin resistant Staphylococcusaureus [8 38] All of the mentioned bacteria are amongthe main causes of nosocomial infections and they havebeen developing antibiotic resistance [59ndash61] Therefore thepotential antibacterial activity of P bleo needs to be furtherinvestigated to identify the lead(s) antibacterial compo-nent(s)
The antifungal activity of the water and methanol extractof P bleo leaves against Cladosporium cucumerinum a plantpathogenic fungus has been reported [43] but they were notactive against Candida albicans a common human pathogen[42 43]
The antiviral properties of the water and methanolextracts of P bleo leaves were evaluated against HerpesSimplex Virus-I (HSV-1) andHuman Immunodeficiency Virus(HIV) by Matsuse et al [62] Both of the extracts demon-strated anti-HIV activity However the result of this studywas not promising because of the low selectivity index of094 Besides in another study by Hattori et al [63] the sameextracts did not demonstrate any antiviral activity againstHSV-1 In general the available data on the antiviral activityof P bleo is neither sufficient nor conclusive Thereforefurther research needs to be carried out
344 Antiparasitic Properties The only antiparasitic inves-tigation on P bleo was reported by Marston et al [52] Intheir study the chloroform methanol and water extractsof this plant did not exert any antiparasitic activity againstschistosomiasis
345 Neutralizing Snake Venom Otero et al [33] evaluatedthe neutralizing effect of the ethanol extract of P bleo onhemorrhagic activity of ldquoBothrops atrox venomrdquo in miceThisextract did not show any neutralizing effect against the testedvenom
346 Antinociceptive Properties Wahab et al [35] evaluatedthe antinociceptive activity of the ethanol extract and itsfractions using two in vivo analgesic models peripheralformalin-induced licking and acetic acid-induced abdominal
writhing They showed that the ethanol extract hexanefraction dichloromethane fraction and ethyl acetate fractionof P bleo had moderate antinociceptive effects However nocompound was identified in their study
35 Toxicity Studies Acute toxicity effect of the leaversquosextracts of P bleo was evaluated by in vitro and in vivostudies Er et al [32] showed that the water extract may formmutagenic compound(s) upon metabolization by the liverenzymes in vitro In another study by Gupta et al [22] themethanol extract of the whole plant had moderate toxicity inbrine shrimp toxicity assay (LD
5077 ppm) In the only in vivo
study by Sim et al [31] the methanol extract did not have anytoxicity effect on ICR mice (LD
50gt 2500mgkg) Although
animalmodels have around 70ndash80 predictability for humantoxicities [64 65] the long term toxicity and themutagenicityof metabolites of P bleo should be further investigated
4 Conclusion
A comprehensive review on Pereskia bleo has been presentedIt provides an overview of the botanical characteristics tra-ditional usage phytoconstituents pharmacological activitiesand safety of P bleo The current review highlights theassociation between the traditional usage of the plant andthe reported anticancer antibacterial and antinociceptiveeffects tested in different studies Although P bleo has beentraditionally used for a variety of therapeutic and prophy-lactic purposes only a few of them has been investigatedHence more research is warranted to further study itsbiological activities and chemical properties to understandits traditional usage and to develop novel therapeuticsUnderstanding the traditional uses knowing the availablescientific evidences and identifying the gaps in research willallow the proper translation of promising research results intoa safe and efficacious usage of herbal medicine and discoveryof new therapeutics It will also assist in setting appropriatepolicy and guidelines in the usage of herbal medicine
Conflict of Interests
All authors declare that there is no conflict of interestsregarding the publication of this paper
Acknowledgments
Funding from the National University of Singapore (NUS)research Grant (R-148-000-137-112 to KHL) and LeewardPacific Pte Ltd (R-148-000-140-592 to KHL) and researchscholarship from the Singapore International GraduateAward (SINGA SZ) are acknowledged
References
[1] C Wiart Medicinal Plants of Asia and the Pacific Drugs of theFuture World Scientific Singapore 2006
[2] N L Britton and J N Rose The Cactaceae Descriptions andIllustrations of Plants of the Cactus Family Dover PublicationsWashington DC USA 2009
10 Evidence-Based Complementary and Alternative Medicine
[3] E J Edwards and M J Donoghue ldquoPereskia and the origin ofthe cactus life-formrdquo American Naturalist vol 167 no 6 pp777ndash793 2006
[4] E J Edwards R Nyffeler and M J Donoghue ldquoBasal cactusphylogeny implications of Pereskia (Cactaceae) paraphyly forthe transition to the cactus life formrdquo American Journal ofBotany vol 92 no 7 pp 1177ndash1188 2005
[5] R M Ogburn and E J Edwards ldquoAnatomical variation in Cac-taceae and relatives trait lability and evolutionary innovationrdquoAmerican Journal of Botany vol 96 no 2 pp 391ndash408 2009
[6] CM Boo C LOu-Yang andKOmar-Hor 1001Garden Plantsin Singapore National Parks Board Singapore 2nd edition2007
[7] Singapore Npark Board NParks FloraampFouna web 2010httpsflorafaunawebnparksgovsgSpecial-Pagesplant-detailaspxid=2324
[8] S I A Wahab A B Abdul S M Mohan A S Al-Zubairi MM Elhassan andMY Ibrahim ldquoBiological activities ofPereskiableo extractsrdquo International Journal of Pharmacology vol 5 no1 pp 71ndash75 2009
[9] R T Barcenas C Yesson and J A Hawkins ldquoMolecular sys-tematics of the CactaceaerdquoCladistics vol 27 no 5 pp 470ndash4892011
[10] K Y Chong H T Tan and R T Corlett A Checklist of theTotal Vascular Plant Flora of Singapore Native Naturalised andCultivated Species Raffles Museum of Biodiversity ResearchNational University of Singapore Singapore 2009 httprmbrnusedusgraffles museum pubflora of singapore tcpdf
[11] A M Sri Nurestri K S Sim and A W Norhanom ldquoPhy-tochemical and cytotoxic investigations of Pereskia grandifoliaHaw (Cactaceae) leavesrdquo Journal of Biological Sciences vol 9no 5 pp 488ndash493 2009
[12] E Anderson The Cactus Family pp 566ndash568 Timber PressPuritana Ore USA 1st edition 2001
[13] R P Wunderlin and B F Hansen ldquoAtlas of Florida VascularPlantsrdquo 2008 httpwwwplantatlasusfedu
[14] N P Taylor D Zappi P Braun and M Machado ldquoPereskiaaculeata Iucn Red List of Threatened Species Version 2013 2rdquo2013 httpwwwiucnredlistorg
[15] E Pooley A Field Guide to Wild Flowers KwaZulu Natal and theEastern Region Natal Flora Publications Trust Durban SouthAfrica 1999
[16] A G I Natural Heritage Trust ldquoWeedManagementGuide Leafcactus Pereskia aculeatardquo 2003 httpwwwenvironmentgovaubiodiversityinvasiveweedspublicationsguidelinesalertpubsp-aculeatapdf
[18] B E Leuenberger ldquoPereskia Maihuenia and Blossfeldia-taxonomic history updates and notesrdquo Haseltonia no 14 pp54ndash93 2008
[19] J Nugent ldquoPermaculture Plants agaves and cactirdquo 2007 httpbooksgooglecomsgbooksid=YVwMM2OdO34Campq=Pereskia+bleov=snippetampq=Pereskia20bleoampf=false
[20] B E Leuenberger ldquoHumboldt amp Bonplandrsquos Cactaceae in theherbaria at Paris and Berlinrdquo Willdenowia vol 32 pp 137ndash1532002
[21] KA LiamasTropical Flowering Plants AGuide to Identificationand Cultivation Timber Press Portland Ore USA 2003
[22] M P Gupta A Monge G A Karikas et al ldquoScreening of Pana-manian medicinal plants for brine shrimp toxicity crown
gall tumor inhibition cytotoxicity and DNA intercalationrdquoPharmaceutical Biology vol 34 no 1 pp 19ndash27 1996
[23] C C Kazama D T Uchida K N Canzi et al ldquoInvolvementof arginine-vasopressin in the diuretic and hypotensive effectsof Pereskia grandifoliaHaw (Cactaceae)rdquo Journal of Ethnophar-macology vol 144 no 1 pp 86ndash93 2012
[25] K S Sim A M Sri Nurestri and A W Norhanom ldquoPhenoliccontent and antioxidant activity of crude and fractionatedextracts of Pereskia bleo (Kunth) DC (Cactaceae)rdquo AfricanJournal of Pharmacy and Pharmacology vol 4 no 5 pp 193ndash201 2010
[26] EMurillo A JMelendez-Martınez and F Portugal ldquoScreeningof vegetables and fruits from Panama for rich sources of luteinand zeaxanthinrdquo Food Chemistry vol 122 no 1 pp 167ndash1722010
[27] K Hostettmann A Marston M Maillard and M HamburgerPhytochemistry of Plants Used in Traditional Medicine pp 373ndash376 Oxford University Press Oxford UK 1995
[28] S N A Malek S K Shin N A Wahab and H Yaacob ldquoCyto-toxic components of Pereskia bleo (Kunth) DC (Cactaceae)leavesrdquoMolecules vol 14 no 5 pp 1713ndash1724 2009
[29] M P Gupta A Correa DMireya et al ldquoMedicinal plant inven-tory of Kuna Indians part 1rdquo Journal of Ethnopharmacology vol40 no 2 pp 77ndash109 1993
[30] A Rahmat F P Saib and N A Buslima ldquoComparing theeffect of ficus benjamina extract and Pereskia saecnarosa extracton tthe level of micro and macro minerals in normal andinduced liver cancer ratsrdquo in Proceedings of the 4th InternationalConference on Biomedical Engineering in Vietnam pp 208ndash2121980
[31] K S Sim A M Sri Nurestri S K Sinniah K H Kim and AW Norhanom ldquoAcute oral toxicity of Pereskia bleo and Pereskiagrandifolia inmicerdquo PharmacognosyMagazine vol 6 no 21 pp67ndash70 2010
[32] H M Er E Cheng and A K Radhakrishnan ldquoAnti-proliferative and mutagenic activities of aqueous and methanolextracts of leaves from Pereskia bleo (Kunth) DC (Cactaceae)rdquoJournal of Ethnopharmacology vol 113 no 3 pp 448ndash456 2007
[33] R Otero V Nunez J Barona et al ldquoSnakebites and ethnob-otany in the northwest region of Colombia part III neutral-ization of the haemorrhagic effect of Bothrops atrox venomrdquoJournal of Ethnopharmacology vol 73 no 1-2 pp 233ndash2412000
[34] P W Doetsch J M Cassady and J L McLaughlin ldquoCac-tus alkaloids XL Identification of mescaline and other 120573-phenethylamines in Pereskia Pereskiopsis and Islaya by use offluorescamine conjugatesrdquo Journal of Chromatography A vol189 no 1 pp 79ndash85 1980
[35] I R A Wahab C C Guilhon P D Fernandes and F BoylanldquoAnti-nociceptive activity of Pereskia bleo Kunth (Cactaceae)leaves extractsrdquo Journal of Ethnopharmacology vol 144 no 3pp 741ndash746 2012
[36] S N AMalek N AWahabH Yaacob et al ldquoCytotoxic activityof Pereskia bleo (Cactaceae) against selected human cell linesrdquoInternational Journal of Cancer Research vol 4 no 1 pp 20ndash272008
Evidence-Based Complementary and Alternative Medicine 11
[37] B Hassanbaglou A A Hamid A Roheeyati et al ldquoAntioxidantactivity of different extracts from leaves of Pereskia bleo (Cac-taceae)rdquo Journal of Meidinal Plants Research vol 6 no 15 pp2932ndash2937 2012
[38] S I Abbdewahab N M Ain A B Abdul M M E Tahaand T A T Ibrahim ldquoEnergy-dispersive X-raymicroanalysis ofelementsrsquo content and antimicrobial properties of Pereskia bleoandGoniothalamus umbrosusrdquoAfrican Journal of Biotechnologyvol 8 no 10 pp 2375ndash2378 2009
[39] S Y Liew E J Stanbridge K Yusoff and N ShafeeldquoHypoxia affects cellular responses to plant extractsrdquo Journal ofEthnopharmacology vol 144 no 2 pp 453ndash456 2012
[40] M L Tan S F Sulaiman N Najimuddin M R Samian and TS T Muhammad ldquoMethanolic extract of Pereskia bleo (Kunth)DC (Cactaceae) induces apoptosis in breast carcinoma T47-D cell linerdquo Journal of Ethnopharmacology vol 96 no 1-2 pp287ndash294 2005
[41] K Philip S N A Malek W Sani et al ldquoAntimicrobial activityof some medicinal plants from Malaysiardquo American Journal ofApplied Sciences vol 6 no 8 pp 1613ndash1617 2009
[42] T Ruegg A I Calderon E F Queiroz et al ldquo3-farnesyl-2-hydroxybenzoic acid is a new anti-Helicobacter pylori com-pound from Piper multiplinerviumrdquo Journal of Ethnopharma-cology vol 103 no 3 pp 461ndash467 2006
[43] L Rahalison M Hamburger K Hostettmann et al ldquoScreeningfor antifungal activity of Panamanian plantsrdquo InternationalJournal of Pharmacognosy vol 31 no 1 pp 68ndash76 1993
[44] A P D Candolle ldquoPereskia bleo (Kunth) DCrdquo 2011 httpwwwtropicosorgName5100482
[47] M Gardener ldquoTropical plants library onlinerdquo 2014 httpmgonlinecomarticlesexoticsaspx
[48] S Kurt ldquoStem of P grandifoliardquo 2014 httpwwwbiolibde[49] NRCS ldquoNatural Resources and Conservation Service of
USDA Plant profile of P grandifolia Hawrdquo 2013 httpplantsusdagovcoreprofilesymbol=PEGR14
[50] D C Sanders A S Grayson andT JMonaco ldquoMineral contentof tomato (Lycopersicon esculentum) and four competing weedspeciesrdquoWeed Science vol 29 no 5 pp 590ndash593 1981
[51] J M Geleijnse J C Witteman A A Bak J H den Breeijenand D E Grobbee ldquoReduction in blood pressure with a lowsodium high potassium high magnesium salt in older subjectswith mild to moderate hypertensionrdquo British Medical Journalvol 309 no 6952 pp 436ndash440 1994
[52] A Marston G Dudan M P Gupta P N Solis M D Correaand K Hostettmann ldquoScreening of Panamanian plants formolluscicidal activityrdquo Pharmaceutical Biology vol 34 no 1 pp15ndash18 1996
[53] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999
[54] T Komiya M Kyohkon S Ohwaki et al ldquoPhytol inducesprogrammed cell death in human lymphoid leukemia Molt 4Bcellsrdquo International Journal of Molecular Medicine vol 4 no 4pp 377ndash380 1999
[55] M Gerber M C Boutron-Ruault S Hercberg E Riboli AScalbert and M H Siess ldquoFood and cancer state of the art
about the protective effect of fruits and vegetablesrdquo Bulletin duCancer vol 89 no 3 pp 293ndash312 2002
[56] V di Matteo and E Esposito ldquoBiochemical and therapeuticeffects of antioxidants in the treatment of Alzheimerrsquos diseaseParkinsonrsquos disease and amyotrophic lateral sclerosisrdquo CurrentDrug Targets-CNSampNeurological Disorders vol 2 no 2 pp 95ndash107 2003
[57] P Knekt R Jarvinen A Reunanen and J Maatela ldquoFlavonoidintake and coronary mortality in Finland a cohort studyrdquoBritish Medical Journal vol 312 no 7029 pp 478ndash481 1996
[58] R A Mustafa A Abdul Hamid S Mohamed and F A BakarldquoTotal phenolic compounds flavonoids and radical scavengingactivity of 21 selected tropical plantsrdquo Journal of Food Sciencevol 75 no 1 pp C28ndashC35 2010
[59] E B Breidenstein C de la Fuente-Nunez and R E HancockldquoPseudomonas aeruginosa all roads lead to resistancerdquo Trendsin Microbiology vol 19 no 8 pp 419ndash426 2011
[60] C Chu C-H ChiuW-YWu C-H Chu T-P Liu and J T OuldquoLarge drug resistance virulence plasmids of clinical isolates ofSalmonella enterica serovar Choleraesuisrdquo Antimicrobial Agentsand Chemotherapy vol 45 no 8 pp 2299ndash2303 2001
[61] K Hiramatsu H Hanaki T Ino K Yabuta T Oguri andF Tenover ldquoMethicillin-resistant Staphylococcus aureus clini-cal strain with reduced vancomycin susceptibilityrdquo Journal ofAntimicrobial Chemotherapy vol 40 no 1 pp 135ndash136 1997
[62] I TMatsuse Y A LimMHattori M Correa andM P GuptaldquoA search for anti-viral properties in Panamanian medicinalplants the effects on HIV and its essential enzymesrdquo Journal ofEthnopharmacology vol 64 no 1 pp 15ndash22 1998
[63] M Hattori T Nakabayashi Y A Lim et al ldquoInhibitory effectsof various Ayurvedic and Panamanian medicinal plants onthe infection of herpes simplex virus-1 in vitro and in vivordquoPhytotherapy Research vol 9 no 4 pp 270ndash276 1995
[64] I Kola and J Landis ldquoCan the pharmaceutical industry reduceattrition ratesrdquoNature Reviews Drug Discovery vol 3 no 8 pp711ndash716 2004
[65] H Olson G Betton D Robinson et al ldquoConcordance ofthe toxicity of pharmaceuticals in humans and in animalsrdquoRegulatory Toxicology and Pharmacology vol 32 no 1 pp 56ndash67 2000
10 Evidence-Based Complementary and Alternative Medicine
[3] E J Edwards and M J Donoghue ldquoPereskia and the origin ofthe cactus life-formrdquo American Naturalist vol 167 no 6 pp777ndash793 2006
[4] E J Edwards R Nyffeler and M J Donoghue ldquoBasal cactusphylogeny implications of Pereskia (Cactaceae) paraphyly forthe transition to the cactus life formrdquo American Journal ofBotany vol 92 no 7 pp 1177ndash1188 2005
[5] R M Ogburn and E J Edwards ldquoAnatomical variation in Cac-taceae and relatives trait lability and evolutionary innovationrdquoAmerican Journal of Botany vol 96 no 2 pp 391ndash408 2009
[6] CM Boo C LOu-Yang andKOmar-Hor 1001Garden Plantsin Singapore National Parks Board Singapore 2nd edition2007
[7] Singapore Npark Board NParks FloraampFouna web 2010httpsflorafaunawebnparksgovsgSpecial-Pagesplant-detailaspxid=2324
[8] S I A Wahab A B Abdul S M Mohan A S Al-Zubairi MM Elhassan andMY Ibrahim ldquoBiological activities ofPereskiableo extractsrdquo International Journal of Pharmacology vol 5 no1 pp 71ndash75 2009
[9] R T Barcenas C Yesson and J A Hawkins ldquoMolecular sys-tematics of the CactaceaerdquoCladistics vol 27 no 5 pp 470ndash4892011
[10] K Y Chong H T Tan and R T Corlett A Checklist of theTotal Vascular Plant Flora of Singapore Native Naturalised andCultivated Species Raffles Museum of Biodiversity ResearchNational University of Singapore Singapore 2009 httprmbrnusedusgraffles museum pubflora of singapore tcpdf
[11] A M Sri Nurestri K S Sim and A W Norhanom ldquoPhy-tochemical and cytotoxic investigations of Pereskia grandifoliaHaw (Cactaceae) leavesrdquo Journal of Biological Sciences vol 9no 5 pp 488ndash493 2009
[12] E Anderson The Cactus Family pp 566ndash568 Timber PressPuritana Ore USA 1st edition 2001
[13] R P Wunderlin and B F Hansen ldquoAtlas of Florida VascularPlantsrdquo 2008 httpwwwplantatlasusfedu
[14] N P Taylor D Zappi P Braun and M Machado ldquoPereskiaaculeata Iucn Red List of Threatened Species Version 2013 2rdquo2013 httpwwwiucnredlistorg
[15] E Pooley A Field Guide to Wild Flowers KwaZulu Natal and theEastern Region Natal Flora Publications Trust Durban SouthAfrica 1999
[16] A G I Natural Heritage Trust ldquoWeedManagementGuide Leafcactus Pereskia aculeatardquo 2003 httpwwwenvironmentgovaubiodiversityinvasiveweedspublicationsguidelinesalertpubsp-aculeatapdf
[18] B E Leuenberger ldquoPereskia Maihuenia and Blossfeldia-taxonomic history updates and notesrdquo Haseltonia no 14 pp54ndash93 2008
[19] J Nugent ldquoPermaculture Plants agaves and cactirdquo 2007 httpbooksgooglecomsgbooksid=YVwMM2OdO34Campq=Pereskia+bleov=snippetampq=Pereskia20bleoampf=false
[20] B E Leuenberger ldquoHumboldt amp Bonplandrsquos Cactaceae in theherbaria at Paris and Berlinrdquo Willdenowia vol 32 pp 137ndash1532002
[21] KA LiamasTropical Flowering Plants AGuide to Identificationand Cultivation Timber Press Portland Ore USA 2003
[22] M P Gupta A Monge G A Karikas et al ldquoScreening of Pana-manian medicinal plants for brine shrimp toxicity crown
gall tumor inhibition cytotoxicity and DNA intercalationrdquoPharmaceutical Biology vol 34 no 1 pp 19ndash27 1996
[23] C C Kazama D T Uchida K N Canzi et al ldquoInvolvementof arginine-vasopressin in the diuretic and hypotensive effectsof Pereskia grandifoliaHaw (Cactaceae)rdquo Journal of Ethnophar-macology vol 144 no 1 pp 86ndash93 2012
[25] K S Sim A M Sri Nurestri and A W Norhanom ldquoPhenoliccontent and antioxidant activity of crude and fractionatedextracts of Pereskia bleo (Kunth) DC (Cactaceae)rdquo AfricanJournal of Pharmacy and Pharmacology vol 4 no 5 pp 193ndash201 2010
[26] EMurillo A JMelendez-Martınez and F Portugal ldquoScreeningof vegetables and fruits from Panama for rich sources of luteinand zeaxanthinrdquo Food Chemistry vol 122 no 1 pp 167ndash1722010
[27] K Hostettmann A Marston M Maillard and M HamburgerPhytochemistry of Plants Used in Traditional Medicine pp 373ndash376 Oxford University Press Oxford UK 1995
[28] S N A Malek S K Shin N A Wahab and H Yaacob ldquoCyto-toxic components of Pereskia bleo (Kunth) DC (Cactaceae)leavesrdquoMolecules vol 14 no 5 pp 1713ndash1724 2009
[29] M P Gupta A Correa DMireya et al ldquoMedicinal plant inven-tory of Kuna Indians part 1rdquo Journal of Ethnopharmacology vol40 no 2 pp 77ndash109 1993
[30] A Rahmat F P Saib and N A Buslima ldquoComparing theeffect of ficus benjamina extract and Pereskia saecnarosa extracton tthe level of micro and macro minerals in normal andinduced liver cancer ratsrdquo in Proceedings of the 4th InternationalConference on Biomedical Engineering in Vietnam pp 208ndash2121980
[31] K S Sim A M Sri Nurestri S K Sinniah K H Kim and AW Norhanom ldquoAcute oral toxicity of Pereskia bleo and Pereskiagrandifolia inmicerdquo PharmacognosyMagazine vol 6 no 21 pp67ndash70 2010
[32] H M Er E Cheng and A K Radhakrishnan ldquoAnti-proliferative and mutagenic activities of aqueous and methanolextracts of leaves from Pereskia bleo (Kunth) DC (Cactaceae)rdquoJournal of Ethnopharmacology vol 113 no 3 pp 448ndash456 2007
[33] R Otero V Nunez J Barona et al ldquoSnakebites and ethnob-otany in the northwest region of Colombia part III neutral-ization of the haemorrhagic effect of Bothrops atrox venomrdquoJournal of Ethnopharmacology vol 73 no 1-2 pp 233ndash2412000
[34] P W Doetsch J M Cassady and J L McLaughlin ldquoCac-tus alkaloids XL Identification of mescaline and other 120573-phenethylamines in Pereskia Pereskiopsis and Islaya by use offluorescamine conjugatesrdquo Journal of Chromatography A vol189 no 1 pp 79ndash85 1980
[35] I R A Wahab C C Guilhon P D Fernandes and F BoylanldquoAnti-nociceptive activity of Pereskia bleo Kunth (Cactaceae)leaves extractsrdquo Journal of Ethnopharmacology vol 144 no 3pp 741ndash746 2012
[36] S N AMalek N AWahabH Yaacob et al ldquoCytotoxic activityof Pereskia bleo (Cactaceae) against selected human cell linesrdquoInternational Journal of Cancer Research vol 4 no 1 pp 20ndash272008
Evidence-Based Complementary and Alternative Medicine 11
[37] B Hassanbaglou A A Hamid A Roheeyati et al ldquoAntioxidantactivity of different extracts from leaves of Pereskia bleo (Cac-taceae)rdquo Journal of Meidinal Plants Research vol 6 no 15 pp2932ndash2937 2012
[38] S I Abbdewahab N M Ain A B Abdul M M E Tahaand T A T Ibrahim ldquoEnergy-dispersive X-raymicroanalysis ofelementsrsquo content and antimicrobial properties of Pereskia bleoandGoniothalamus umbrosusrdquoAfrican Journal of Biotechnologyvol 8 no 10 pp 2375ndash2378 2009
[39] S Y Liew E J Stanbridge K Yusoff and N ShafeeldquoHypoxia affects cellular responses to plant extractsrdquo Journal ofEthnopharmacology vol 144 no 2 pp 453ndash456 2012
[40] M L Tan S F Sulaiman N Najimuddin M R Samian and TS T Muhammad ldquoMethanolic extract of Pereskia bleo (Kunth)DC (Cactaceae) induces apoptosis in breast carcinoma T47-D cell linerdquo Journal of Ethnopharmacology vol 96 no 1-2 pp287ndash294 2005
[41] K Philip S N A Malek W Sani et al ldquoAntimicrobial activityof some medicinal plants from Malaysiardquo American Journal ofApplied Sciences vol 6 no 8 pp 1613ndash1617 2009
[42] T Ruegg A I Calderon E F Queiroz et al ldquo3-farnesyl-2-hydroxybenzoic acid is a new anti-Helicobacter pylori com-pound from Piper multiplinerviumrdquo Journal of Ethnopharma-cology vol 103 no 3 pp 461ndash467 2006
[43] L Rahalison M Hamburger K Hostettmann et al ldquoScreeningfor antifungal activity of Panamanian plantsrdquo InternationalJournal of Pharmacognosy vol 31 no 1 pp 68ndash76 1993
[44] A P D Candolle ldquoPereskia bleo (Kunth) DCrdquo 2011 httpwwwtropicosorgName5100482
[47] M Gardener ldquoTropical plants library onlinerdquo 2014 httpmgonlinecomarticlesexoticsaspx
[48] S Kurt ldquoStem of P grandifoliardquo 2014 httpwwwbiolibde[49] NRCS ldquoNatural Resources and Conservation Service of
USDA Plant profile of P grandifolia Hawrdquo 2013 httpplantsusdagovcoreprofilesymbol=PEGR14
[50] D C Sanders A S Grayson andT JMonaco ldquoMineral contentof tomato (Lycopersicon esculentum) and four competing weedspeciesrdquoWeed Science vol 29 no 5 pp 590ndash593 1981
[51] J M Geleijnse J C Witteman A A Bak J H den Breeijenand D E Grobbee ldquoReduction in blood pressure with a lowsodium high potassium high magnesium salt in older subjectswith mild to moderate hypertensionrdquo British Medical Journalvol 309 no 6952 pp 436ndash440 1994
[52] A Marston G Dudan M P Gupta P N Solis M D Correaand K Hostettmann ldquoScreening of Panamanian plants formolluscicidal activityrdquo Pharmaceutical Biology vol 34 no 1 pp15ndash18 1996
[53] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999
[54] T Komiya M Kyohkon S Ohwaki et al ldquoPhytol inducesprogrammed cell death in human lymphoid leukemia Molt 4Bcellsrdquo International Journal of Molecular Medicine vol 4 no 4pp 377ndash380 1999
[55] M Gerber M C Boutron-Ruault S Hercberg E Riboli AScalbert and M H Siess ldquoFood and cancer state of the art
about the protective effect of fruits and vegetablesrdquo Bulletin duCancer vol 89 no 3 pp 293ndash312 2002
[56] V di Matteo and E Esposito ldquoBiochemical and therapeuticeffects of antioxidants in the treatment of Alzheimerrsquos diseaseParkinsonrsquos disease and amyotrophic lateral sclerosisrdquo CurrentDrug Targets-CNSampNeurological Disorders vol 2 no 2 pp 95ndash107 2003
[57] P Knekt R Jarvinen A Reunanen and J Maatela ldquoFlavonoidintake and coronary mortality in Finland a cohort studyrdquoBritish Medical Journal vol 312 no 7029 pp 478ndash481 1996
[58] R A Mustafa A Abdul Hamid S Mohamed and F A BakarldquoTotal phenolic compounds flavonoids and radical scavengingactivity of 21 selected tropical plantsrdquo Journal of Food Sciencevol 75 no 1 pp C28ndashC35 2010
[59] E B Breidenstein C de la Fuente-Nunez and R E HancockldquoPseudomonas aeruginosa all roads lead to resistancerdquo Trendsin Microbiology vol 19 no 8 pp 419ndash426 2011
[60] C Chu C-H ChiuW-YWu C-H Chu T-P Liu and J T OuldquoLarge drug resistance virulence plasmids of clinical isolates ofSalmonella enterica serovar Choleraesuisrdquo Antimicrobial Agentsand Chemotherapy vol 45 no 8 pp 2299ndash2303 2001
[61] K Hiramatsu H Hanaki T Ino K Yabuta T Oguri andF Tenover ldquoMethicillin-resistant Staphylococcus aureus clini-cal strain with reduced vancomycin susceptibilityrdquo Journal ofAntimicrobial Chemotherapy vol 40 no 1 pp 135ndash136 1997
[62] I TMatsuse Y A LimMHattori M Correa andM P GuptaldquoA search for anti-viral properties in Panamanian medicinalplants the effects on HIV and its essential enzymesrdquo Journal ofEthnopharmacology vol 64 no 1 pp 15ndash22 1998
[63] M Hattori T Nakabayashi Y A Lim et al ldquoInhibitory effectsof various Ayurvedic and Panamanian medicinal plants onthe infection of herpes simplex virus-1 in vitro and in vivordquoPhytotherapy Research vol 9 no 4 pp 270ndash276 1995
[64] I Kola and J Landis ldquoCan the pharmaceutical industry reduceattrition ratesrdquoNature Reviews Drug Discovery vol 3 no 8 pp711ndash716 2004
[65] H Olson G Betton D Robinson et al ldquoConcordance ofthe toxicity of pharmaceuticals in humans and in animalsrdquoRegulatory Toxicology and Pharmacology vol 32 no 1 pp 56ndash67 2000
Evidence-Based Complementary and Alternative Medicine 11
[37] B Hassanbaglou A A Hamid A Roheeyati et al ldquoAntioxidantactivity of different extracts from leaves of Pereskia bleo (Cac-taceae)rdquo Journal of Meidinal Plants Research vol 6 no 15 pp2932ndash2937 2012
[38] S I Abbdewahab N M Ain A B Abdul M M E Tahaand T A T Ibrahim ldquoEnergy-dispersive X-raymicroanalysis ofelementsrsquo content and antimicrobial properties of Pereskia bleoandGoniothalamus umbrosusrdquoAfrican Journal of Biotechnologyvol 8 no 10 pp 2375ndash2378 2009
[39] S Y Liew E J Stanbridge K Yusoff and N ShafeeldquoHypoxia affects cellular responses to plant extractsrdquo Journal ofEthnopharmacology vol 144 no 2 pp 453ndash456 2012
[40] M L Tan S F Sulaiman N Najimuddin M R Samian and TS T Muhammad ldquoMethanolic extract of Pereskia bleo (Kunth)DC (Cactaceae) induces apoptosis in breast carcinoma T47-D cell linerdquo Journal of Ethnopharmacology vol 96 no 1-2 pp287ndash294 2005
[41] K Philip S N A Malek W Sani et al ldquoAntimicrobial activityof some medicinal plants from Malaysiardquo American Journal ofApplied Sciences vol 6 no 8 pp 1613ndash1617 2009
[42] T Ruegg A I Calderon E F Queiroz et al ldquo3-farnesyl-2-hydroxybenzoic acid is a new anti-Helicobacter pylori com-pound from Piper multiplinerviumrdquo Journal of Ethnopharma-cology vol 103 no 3 pp 461ndash467 2006
[43] L Rahalison M Hamburger K Hostettmann et al ldquoScreeningfor antifungal activity of Panamanian plantsrdquo InternationalJournal of Pharmacognosy vol 31 no 1 pp 68ndash76 1993
[44] A P D Candolle ldquoPereskia bleo (Kunth) DCrdquo 2011 httpwwwtropicosorgName5100482
[47] M Gardener ldquoTropical plants library onlinerdquo 2014 httpmgonlinecomarticlesexoticsaspx
[48] S Kurt ldquoStem of P grandifoliardquo 2014 httpwwwbiolibde[49] NRCS ldquoNatural Resources and Conservation Service of
USDA Plant profile of P grandifolia Hawrdquo 2013 httpplantsusdagovcoreprofilesymbol=PEGR14
[50] D C Sanders A S Grayson andT JMonaco ldquoMineral contentof tomato (Lycopersicon esculentum) and four competing weedspeciesrdquoWeed Science vol 29 no 5 pp 590ndash593 1981
[51] J M Geleijnse J C Witteman A A Bak J H den Breeijenand D E Grobbee ldquoReduction in blood pressure with a lowsodium high potassium high magnesium salt in older subjectswith mild to moderate hypertensionrdquo British Medical Journalvol 309 no 6952 pp 436ndash440 1994
[52] A Marston G Dudan M P Gupta P N Solis M D Correaand K Hostettmann ldquoScreening of Panamanian plants formolluscicidal activityrdquo Pharmaceutical Biology vol 34 no 1 pp15ndash18 1996
[53] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999
[54] T Komiya M Kyohkon S Ohwaki et al ldquoPhytol inducesprogrammed cell death in human lymphoid leukemia Molt 4Bcellsrdquo International Journal of Molecular Medicine vol 4 no 4pp 377ndash380 1999
[55] M Gerber M C Boutron-Ruault S Hercberg E Riboli AScalbert and M H Siess ldquoFood and cancer state of the art
about the protective effect of fruits and vegetablesrdquo Bulletin duCancer vol 89 no 3 pp 293ndash312 2002
[56] V di Matteo and E Esposito ldquoBiochemical and therapeuticeffects of antioxidants in the treatment of Alzheimerrsquos diseaseParkinsonrsquos disease and amyotrophic lateral sclerosisrdquo CurrentDrug Targets-CNSampNeurological Disorders vol 2 no 2 pp 95ndash107 2003
[57] P Knekt R Jarvinen A Reunanen and J Maatela ldquoFlavonoidintake and coronary mortality in Finland a cohort studyrdquoBritish Medical Journal vol 312 no 7029 pp 478ndash481 1996
[58] R A Mustafa A Abdul Hamid S Mohamed and F A BakarldquoTotal phenolic compounds flavonoids and radical scavengingactivity of 21 selected tropical plantsrdquo Journal of Food Sciencevol 75 no 1 pp C28ndashC35 2010
[59] E B Breidenstein C de la Fuente-Nunez and R E HancockldquoPseudomonas aeruginosa all roads lead to resistancerdquo Trendsin Microbiology vol 19 no 8 pp 419ndash426 2011
[60] C Chu C-H ChiuW-YWu C-H Chu T-P Liu and J T OuldquoLarge drug resistance virulence plasmids of clinical isolates ofSalmonella enterica serovar Choleraesuisrdquo Antimicrobial Agentsand Chemotherapy vol 45 no 8 pp 2299ndash2303 2001
[61] K Hiramatsu H Hanaki T Ino K Yabuta T Oguri andF Tenover ldquoMethicillin-resistant Staphylococcus aureus clini-cal strain with reduced vancomycin susceptibilityrdquo Journal ofAntimicrobial Chemotherapy vol 40 no 1 pp 135ndash136 1997
[62] I TMatsuse Y A LimMHattori M Correa andM P GuptaldquoA search for anti-viral properties in Panamanian medicinalplants the effects on HIV and its essential enzymesrdquo Journal ofEthnopharmacology vol 64 no 1 pp 15ndash22 1998
[63] M Hattori T Nakabayashi Y A Lim et al ldquoInhibitory effectsof various Ayurvedic and Panamanian medicinal plants onthe infection of herpes simplex virus-1 in vitro and in vivordquoPhytotherapy Research vol 9 no 4 pp 270ndash276 1995
[64] I Kola and J Landis ldquoCan the pharmaceutical industry reduceattrition ratesrdquoNature Reviews Drug Discovery vol 3 no 8 pp711ndash716 2004
[65] H Olson G Betton D Robinson et al ldquoConcordance ofthe toxicity of pharmaceuticals in humans and in animalsrdquoRegulatory Toxicology and Pharmacology vol 32 no 1 pp 56ndash67 2000
