JOURNAL OF NATURAL REMEDIES * Corresponding author Email: [email protected]1. Introduction Salacia is a climbing shrub, distributed in South – West India, Peninsula, Ceylon, Java, Thailand and Philippines [1]. Within India, it is distributed in Karnataka (rare in semi-evergreen forests of Western Ghats), Kerala (coastal forests of Kollam, Western Ghats of Pathanamthitta and Idukki districts) and Southern Orissa [2]. In the Traditional System of Medicine, the plants of this genus are being used as acrid, bitter, thermogenic, urinary, astringent, anodyne, anti-inflammatory, depurative, emmenagogue, vulnerary, liver tonic and stomachic. They are useful in vitiates conditions of vata, diabetes, hemorrhoids, inflammation, leucorrhoea, leprosy, skin diseases, amenorrhoea, dysmenorrhoea, wounds, ulcers, hyperhydrosis, hepatopathy, dyspepsia, flatulence, colic, and spermatorrhoea [3]. The present aim is to give a comprehensive review about macroscopical characteristics, phytochemical and pharmacological activities reported so far from this genus. The genus Salacia comprises of 100 species, out of which, in India, Salacia reticulata and Salacia oblonga are predominant species (4). 1.1 Taxonomical / Scientific Classification [5] Kingdom: Plantae - Planta, plantes, plants, vegetal Genus Salacia: A Comprehensive Review Padmaa M. Paarakh 1 *, Leena J. Patil 2 , S. Angelin Thanga 3 1. Department of Pharmacognosy, The Oxford College of Pharmacy, Bangalore 560078, Karnataka, India. 2. Department of Pharmacology, The Oxford College of Pharmacy, Bangalore 560078, Karnataka, India. 3. Department of Pharmaceutics, The Oxford College of Pharmacy, Bangalore 560078, Karnataka, India. Abstract Salacia sps (Family: Celastraceae / Hippocrateaceae) is an important source of chemicals of immense medicinal and pharmaceutical importance such as salacinol, mangiferin and kotanalol which are effective as antidiabetic, antiobese, hepatoprotective, hypolipidemic and antioxidant agent. Hence, this review considers the importance of the genus Salacia and an attempt is made to present macroscopical, phytochemical and pharmacological activities of the genus Salacia. Key words: Salacia sps; Macroscopical; Phytochemical; Pharmacological activity Vol. 8/2 (2008) 116 - 131
Salacia is a climbing shrub, distributed inSouth – West India, Peninsula, Ceylon, Java,Thailand and Philippines [1]. Within India, it isdistributed in Karnataka (rare in semi-evergreenforests of Western Ghats), Kerala (coastalforests of Kollam, Western Ghats ofPathanamthitta and Idukki districts) andSouthern Orissa [2]. In the Traditional Systemof Medicine, the plants of this genus are beingused as acrid, bitter, thermogenic, urinary,astringent, anodyne, anti-inflammatory,depurative, emmenagogue, vulnerary, liver tonicand stomachic. They are useful in vitiatesconditions of vata, diabetes, hemorrhoids,
inflammation, leucorrhoea, leprosy, skindiseases, amenorrhoea, dysmenorrhoea,wounds, ulcers, hyperhydrosis, hepatopathy,dyspepsia, flatulence, colic, and spermatorrhoea[3]. The present aim is to give a comprehensivereview about macroscopical characteristics,phytochemical and pharmacological activitiesreported so far from this genus. The genusSalacia comprises of 100 species, out of which,in India, Salacia reticulata and Salacia oblongaare predominant species (4).
Genus Salacia: A Comprehensive ReviewPadmaa M. Paarakh 1*, Leena J. Patil 2, S. Angelin Thanga 3
1. Department of Pharmacognosy, The Oxford College of Pharmacy, Bangalore 560078, Karnataka, India.
2. Department of Pharmacology, The Oxford College of Pharmacy, Bangalore 560078, Karnataka, India.
3. Department of Pharmaceutics, The Oxford College of Pharmacy, Bangalore 560078, Karnataka, India.
Abstract
Salacia sps (Family: Celastraceae / Hippocrateaceae) is an important source of chemicals of immense medicinal andpharmaceutical importance such as salacinol, mangiferin and kotanalol which are effective as antidiabetic, antiobese,hepatoprotective, hypolipidemic and antioxidant agent. Hence, this review considers the importance of the genusSalacia and an attempt is made to present macroscopical, phytochemical and pharmacological activities of thegenus Salacia.
The general macroscopical characteristics of theplants of the genus are as follows, scandent orsarmentosa shrub or small tree. Leaves usuallyopposite, petioled, coriaceous, shinning above,exstipulate. Flowers small, axillary or extra-axillary, fascicled or cymose, rarely solitary or2-Nate. Calyx small, 5-partite. Petals 5,spreading, imbricate. Stamens 3 (very rarely 2or 4), inserted on the disk, free or connate withthe ovary; filament conniving at the apex,
recurved; anthers small, dehiscing extrorsely,adnate, 2- celled, lobes divaricating at the base.Disk thick, sinuate, ovary sunk in the disk,conical, 3-celled; ovules 2, 4 or more in eachcell, affixed to the axis, 1 or 2 seriate; styleusually very short; stigma simple or 3 lobed.Fruit baccate, edible, 1-3 celled; cells 1-4seeded; rind coriaceous or sub woody; pulpmucilaginous. Seeds large, angular; testa ratherthick, coriaceous or fibrous; cotyledons thick,usually conferruminate [6, 7, 8].
1.3 Phytochemistry
Salacia species are known to elaborateanthocyanidines, catechins, phenolic acids,quinones, friedo-oleanones, quinonemethide andrelated triterpenoids (celastroloids), mangiferin,gutta percha and dulcitol. The major bioactiveconstituents are being xanthine, glucoside,mangiferin and two components with uniquethiosugar structure sulfonium sulfate viz.,salacinol and kotalanol. The phytoconstitutentsisolated so far from different species of the genusis given below:
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Sl Species Constitutents Isolated Parts Ref.No.
1. S. reticulata Mangiferin Root 9
2. S. reticulata Kotanolol Root and stem 10
3. S. reticulata (-)-Epicatechin; (-)-epigallocatechin; (-)-4'-O-methylepigallocatechin; Root 11(-)-epiafzelechin-(4ß 8)-(-)-4'-O-methylepigallocatechin;(-)-epicathechin-(4ß 8)-(-)-4'-O-methylepigallocatechin
29. S. chinensis FoliasalaciosidesA1, A2, B1, B2, C, D, E1, F1, F2, F3,F4, F5, F6 and F7 Leaves 37
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1.4 Pharmacological Activity
1.4.1 Antidiabetic Activity
The aqueous decoction of 40 plants wereinvestigated for their hypoglycemic activity inSprague-Dawley rats by Karunanayake andcoworkers [38] for their ability to lower thefasting blood glucose level and improve theglucose tolerance in animals. Maximumreduction in blood glucose level (30%) wasobserved 3 hours after administration ofS.reticulata aqueous decoction and whichpersisted up to 5 hours suggesting itshypoglycemic potential.
Serasinghe and coworkers demonstratedantidiabetic activity in streptozotocin induceddiabetic rats. Reduction in plasma glucose levelswere observed in 0.5 g/kg, 1.0 g/kg and 5.0 g/kg doses of S.reticulata by 42.8%, 45.4% and87.5% respectively (39).
Shimoda investigated the effect of an aqueousextract of the stems of S.reticulata (SI) on postprandial hyperglycemia in rats and humans.In a dose dependent manner, SI extractsuppressed an increase in serum glucose levelswhen fed with sucrose, maltose and starch. Inaddition, extract strongly inhibited the
activities of -glucosidase prepared from theyeast and rat jejunum with IC50 value of 5 and8 µg/ml respectively. In the sucrose tolerancetest, the aqueous extract of roots of S.reticulata(200 mg) given 5 minutes before sucroseloading (50 gm) significantly suppressed postprandial hyperglycemia in healthy humanvolunteers [40, 41].
Jayawardena and coworkers conducted arandomized double blind clinical trial toinvestigate the effect of an herbal tea containingS.reticulata in patients with type II Diabetesmellitus as assessed by HbA1C. A statisticallysignificant fall in HbA1C was seen withtea compared to a rise in HbA1C with theplacebo group which concludes that tea isan effective and safe treatment for type IIdiabetes [42].
Kajimoto and coworkers have investigated theeffect of an aqueous extract from the stem ofS.reticulata for the prevention of type 2 diabetesin a placebo controlled cross-over trial. Therewas significant reduction in fasting plasmaglucose level, HbA1C and BMI suggesting theuse of S.reticulata diet for individuals with mildtype 2 diabetes [43].
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Fig. 1: Salacia oblonga
Rabbani and coworkers have shown that hydroalcoholic extract of S.reticulata at the dose of500 mg/kg p.o. reduced significantly the serumglucose level when compared to the controlgroup in hydrocortisone induced hypoglycemiamodel [44].
Yoshikawa and coworkers discovered that awater soluble fraction (25-100 mg/kg per orally)prepared from the roots and stems ofS.reticulata strongly inhibited elevated serumglucose level after the administration of sucroseor maltose. In addition, the fraction inhibitedrat intestinal maltose and sucrose in in vitro testwith IC50 value of 35 µg/ml and 26 µg/mlrespectively [12].
To confirm this activity, Yoshikawa andcoworkers performed a bioassay guidedseparation to isolate salacinol which showedcompetitive inhibition of intestinal -glucosidase in vitro. The IC50 values were 3.2µg/ml, 0.84 µg/ml and 0.59 µg/ml for maltase,sucrase and isomaltase respectively. Theinhibitory action against maltase and sucrasewas almost equal to that of acarbose (aclinically used -glucosidase inhibitor) butmore potent than acarbose against isomaltase.In addition to this, the inhibitory effect ofsalacinol on serum glucose levels in maltoseand sucrose loaded rats were found to be morepotent than that of acarbose [12].
Yoshikowa and coworkers further isolatedkotanalol by bioassay guided fractionationwhich showed more potent inhibitory activityagainst sucrase. The IC50 values were 2.8 µg/ml, 0.58 µg/ml and 1.9 µg/ml for maltase,sucrase and isomaltase respectively [10].
Yoshikawa and coworkers further studied theinhibitory effect of mangiferin againstcarbohydrate metabolizing enzymes, sucrase,maltase, isomaltase, -amylase and aldosereductase and compared it with salacinol and
kotanalol. Magniferin inhibited - glucosidase,sucrase, isomaltase and also aldose reductaseactivities which were not seen with kotanololand salacinol. S.reticulata extract effectivelyinhibited -amylase activity (derived fromprocaine pancreas) in a dose dependant mannerwith 68.55% inhibition at a concentration of35µg/ml [11].
Minami and coworkers have demonstrated thatdesulfonated derivative of salacinol isolatedfrom the roots of S.oblonga as a potentinhibitor of isomaltase with IC50 value of0.64 mM [45].
In an animal model (KK-Ay mice) of type 2diabetes, magniferin and its glucosides loweredblood glucose level at a dose of 30 mg/kg p.o.for two weeks and significantly improvedhyperinsulinemia, which concluded thatmagniferin probably decreasse blood sugar levelthrough decreasing insulin resistance [46].
Venkateswarlu and coworkers investigated theantidiabetic activity of various fractions of thealcoholic extract of the roots of S.macrospermain alloxan-diabetic rats. The methanolic fractionfollowed by the residual fractionation of thealcoholic extract exhibited significantantidiabetic activity. This activity may be dueto their insulin-like properties [47].
Pillai and coworkers have demonstratedthe hypoglycemic activity of root bark of S.prenoides against alloxan induced diabetes inrats proving its potential as antidiabetic plant[48]. Augusti and coworkers have isolated twocompounds from the root bark of S.oblongafrom chloroform eluted fraction of thepetroleum ether extract and a fluorescentcompound which demonstrated about 60% and76% hypoglycemic activity in comparison toan equal dose of tolbutamide (250 mg/kg) inalbino rats. The results indicate the therapeuticimportance of S.oblonga [49].
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Matsuda and coworkers have evaluated theinhibitory activity of aqueous methanolic extractof roots of S.oblonga on increased serum glucoselevel in sucrose- and maltose-loaded rats. Thewater- and ethyl acetate-soluble portions fromthe aqueous methanolic extract showedinhibitory activities on -glucosidase and aldosereductase respectively [19].
Krishnakumar and coworkers have studied theeffect of petroleum ether extract of root barkof S.oblonga (SOB) in streptozotocin (STZ)diabetic rats. SOB prevented significantly thestreptozotocin-induced hyperglycemia andhypoinsulinaemia suggesting that S.oblongaroot bark extract possesses anti-diabeticactivity [50].
Morikawa and coworkers have shown that sixconstituents viz., 3, 22-dihydroxyolean-12-en-29-oic acid, tingenone, tingenine B, regeolA, triptocalline A, and mangiferin, fromS.chinensis were found to show an inhibitoryeffect on rat aldose reductase suggesting itsantidiabetic potential [32].
Yoshikawa and coworkers have studied theantidiabetogenic activity of methanolic extractfrom the stems of S.chinensis and showed potentanti-hyperglycemic effects in oral sucrose ormaltose-loaded rats, inhibitory effects onintestinal -glucosidase, rat aldose reductase,formation of Amadori compounds and advancedglycation end-products [33].
Matsuda and coworkers have studied theinhibitory effects on the intestinal digestion andabsorption of sugar from health tea which isused for controlling diabetes. The duration ofthe inhibitory effect on the sucrose load ofS.oblonga tea was found to be 110 min [51].
The effect of different doses of S.oblonga extract(0, 500, 700, or 1000 mg) on postprandialglycemic, insulinemic and breath hydrogenresponses in healthy adults were studied byHeacock and coworkers. When compared with
the control, the 1000 mg dose of S.oblongaextract reduced the plasma glucose and seruminsulin (0 to 120 minutes postprandial) by 23%and 29% respectively. The other doses ofS.oblonga extract did not have significantcontrol on glycemia or insulinemia. Breathhydrogen excretion increased linearly as the doseof S.oblonga extract was increased [52].
Collene and coworkers studied the postprandialglycemic, insulinemic and breath hydrogenresponses to a liquid nutritional productcontaining S.oblonga extract (100 mg; SOE) andtwo insulinogenic amino acids phenylalanine andleucine. S.oblonga extract was found to be apromising nutraceutical ingredient as it decreasedglycemia (decrease in plasma glucose level andinsulin level) and breath hydrogen excretion was60% greater in the SOE-containing meals.Supplementation with amino acids had nosignificant additional effect on glycemia [53].
Li and coworkers have studied the effect of waterextract of S.oblonga on the cardiac complicationswith diabetic patients on cardiac fibrosis andhyperglycemia in a genetic model of type 2diabetes, the obese Zucker rats (OZR). Chronicadministration of the extract markedly improvedinterstitial and perivascular fibrosis in the heartsof the OZR. It also reduced plasma glucose levelsin non-fasted OZR; whereas it had little effect inthe fasted animals, suggesting inhibition ofpostprandial hyperglycemia in type 2 diabeticanimals which play a role in improvement of thecardiac complications of OZR [54]. S.oblongaroot improves cardiac lipid metabolism in Zuckerdiabetic fatty rats (ZDF), a genetic model of type2 diabetes and obesity by modulation of cardiacPPAR-alpha-mediated transcription of fatty acid(FA) metabolic genes was studied by Huang andcoworkers. Chronic oral administration ofS.oblonga extract (SOE) reduces cardiactriglyceride and FA contents and decreased theOil red O-stained area in the myocardium of ZDFrats, which parallels the effects on plasmatriglyceride and FA levels [55].
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Furthermore, the treatment suppressed cardiacover expression of both FA transporter protein-1 mRNA and protein in ZDF rats, suggestinginhibition of increased cardiac FA uptake as thebasis for decreased cardiac FA levels. Theseresults suggest that SOE inhibits excess cardiaclipid accumulation and increased cardiac FAoxidation in diabetes and obesity which occursby reduction of cardiac FA uptake, therebymodulating cardiac PPAR-alpha-mediated FAmetabolic gene transcription [55].
Further the same workers have evaluatedantidiabetic and antiobesity activity on chronicoral administration of the water extract ofS.oblonga root in ZDF. The extract loweredplasma triglyceride and total cholesterol levels,increased plasma high-density lipoprotein levelsand reduced the liver contents of triglyceride,non-esterified fatty acids and the ratio offatty droplets to total tissue. These findingssuggest that S.oblonga extract functions as aPPAR-alpha activator, providing a potentialmechanism for improvement of postprandialhyperlipidemia and hepatic steatosis in diabetesand obesity [56].
Shimoda and coworkers have shown that anaqueous extract from S.reticulata when fed withcommercial diet containing 0.05 or 0.1 % extractfor 3 weeks lowered the serum triglycerides levelwhich is attributed to decrease in absorption ofsugar which is the source of triglycerides invivo [57].
Willam and coworkers have studied the effectof S.oblonga extract (240 mg and 480 mg) onpostprandial glycemia and insulinemia in patientswith type 2 diabetes after ingestion of a high-carbohydrate meal. Both doses of the Salaciaextract significantly lowered the postprandialpositive area under the glucose curve (14 % forthe 240 mg extract and 22 % for the 480 mgextract) and the adjusted peak glucose response(19 % for the lower dose and 27 % for the higher
dose of extract) compared to the control meal.The results suggest that Salacia may bebeneficial for postprandial glucose control [58].
Huang and coworkers have investigated theeffect of the water extract of S.oblonga (SOE)on obesity and diabetes-associated cardiachypertrophy and discussed the role ofmodulation of cardiac angiotensin II type 1receptor (AT(1)) expression in the effect. SOEtreatment suppressed cardiac over expressionof atrial natriuretic peptide (ANP), brainnatriuretic peptide (BNP) and AT (1) mRNAsand AT (1) protein in ZDF rats. SOE (50-100g/ml) and mangiferin (25 mol) suppressedangiotensin II-induced ANP mRNA overexpression and protein synthesis in H9c2 cells.They also inhibited angiotensin II-stimulated [3H]thymidine incorporation by cardiac fibroblastswhich demonstrated that SOE decreases cardiachypertrophy in ZDF rats at least in part byinhibiting cardiac AT(1) over expression [59].
Umamaheswari and coworkers have evaluatedthe antihyperglycemic effect of ‘Ilogen-Excel’in streptozotocin induced diabetic rats. Oraladministration of ‘Ilogen-Excel’ (50 mg/kg and100 mg/kg) for 60 days resulted in significantlylowered levels of blood glucose and increasedlevels of plasma insulin, hepatic glycogen andtotal haemoglobin, decreased plasmathiobarbituric acid reactive substances,hydroperoxides, ceruloplasmin and vitamin E indiabetic rats. It was proved that combinedtherapy is better than individual therapy in STZinduced diabetic rats [60].
1.4.2 Hepatoprotective and antioxidant activity
The hepatoprotective effect of the hot water(SRHW) and methanolic (SRM) extracts fromthe roots and stems of S. reticulata were examinedby Yoshikawa and coworkers using an oxidativestress-induced liver injury model. Both SRHWand SRM extracts (400 mg/kg, p.o.) significantly
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suppressed the increase in glutamic oxaloacetictransaminase (GOT) and glutamic pyruvictransaminase (GPT) activities in carbontetrachloride (CCl4) treated mice. These extractsalso inhibited CCl4 induced thiobarbituric acidreactive substance (TBARS) formation whichindicates increased lipid peroxidation in the liversuggesting its hepatoprotective activity [61].
Rong and coworkers have demonstrated thatan aqueous extract of S.oblonga root at thedoses of 100, 300 and 900 mg/Kg, p.o. oncedaily for 28 days induced gender dependenthepatic hypertrophy in rats which is attributedto the sex hormones in both male and femalerats. There was dose dependent increase in liverweight in both male and female rats but lesspredominant in female rats. It was found toactivate PPAR-alpha in human hepatoma derivedHepG2 cells by upregulation of PPAR-alpha andacyl-CoA oxidase in RNA expression [62].
1.4.3 Antioxidant activity
The antioxidative activity of mangiferin, (-)-4`-O-methylepigallocatechin and (-)-epicatechin-(48)-(-)-4`-O-methylepigallocatechin fromthe roots of S.reticulata were examined. Theyshowed potent scavenging activity of DPPHradicals and their IC50 values were 5.9, 10 and3.2 µM respectively [61]. The free-radicalscavenging activities of the quinonemethidetriterpenes salacin, pristimerin, maytenin, 20 -hydroxymaytenin and netzahualcoyene haveshown 19, 20, 39, 28, 55 and 10 % inhibitionof DPPH radical respectively was studied byCarvalho and coworkers [36].
Salaquinone B and catechin isolated from stemsof S.chinensis have been reported to have radicalscavenging activity against DPPH with 40 and70 % inhibition respectively [31].
Krishnakumar and coworkers have shown thatS. oblonga root (SOB) extract possess anti-lipidperoxidative activity in the cardiac tissue ofstreptozotocin (STZ) diabetic rats. SOB produced
a significant decrease in peroxidation productsviz., thiobarbituric acid reactive substances,conjugated dienes and hydroperoxides. Theactivity of antioxidant enzymes such as superoxidedismutase, catalase, GSHPxase and GSSGRasewere increased in the heart tissue of diabeticanimals treated with SOB suggesting itsantioxidant activity [50, 81].
Nitric oxide production from lipopolysaccharide-activated mouse peritoneal macrophage andradical scavenging activities of the methanolicextract of S. chinensis which proved that it haspotent antioxidant activity was studied byYoshikawa and coworkers [33].
1.4.4 Antimicrobial activity
Antimicrobial activity of chloroform andmethanolic extracts of S.reticulata were testedagainst Staphylococcus aureus, Bacillus subtilis,Pseudomonas auerginosa, Escheria coli andfungal strains viz., Cryptococcus neoformans,Candida tropicalis, Candida albicans andEpidermophyton floccosum using zone ofinhibition and MIC was reported by Choudharyand coworkers. It was observed that bothextracts have inhibitory effects towards allmicroorganisms used in the test. However,chloroform extract was more effective thanmethanolic extract [63].
Samy reported the antimicrobial activity of themethanolic extract of S.macrosperma. It wasfound to be very effective against the testmicroorganism [64].
Deepa and Narmathabai have investigated theantibacterial activity of petroleum ether, ethylacetate and chloroform extract of leaves andstems of S.beddomei. Ethyl acetate extracts wasfound to be most effective against all the testedorganisms [65]. Setzer and coworkers havedemonstrated the antibacterial activity ofS.petenensis which led to the isolation oftingenone and netzahualcyenol as biologicallyactive compounds against test microorganismused [30].
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1.4.5 Cytotoxic activity
Setzer and coworkers has studied the cytotoxicactivity of crude dichloromethane bark extractof S.petensis, which subjected to bioactivityguided fraction led to the isolation of tingenoneand netzahyualcyenol. The possible mode ofcytotoxic action of quinone-methidetriterpenoids involves quasi-intercalativeinteraction of the compounds with DNAfollowed by nucleophilic addition of the DNAbase to carbon-6 of the triterpenoid [30].
Augusti and coworkers have demonstrated thecytotoxic activity of petroleum ether extract ofthe root bark of S.oblonga against Ehrlich ascitestumor cells. The methanol eluted fraction ofthe petroleum ether extract (50 g/ml) showed100 percent cytotoxicity on Ehrlich ascitestumour cells [49]. Figueiredo and coworkershave shown that the compounds 28-nor-isoiguesterin-17 carbaldehyde, 17-(methoxycarbonyl)-28-nor-isoiguesterin, 28-hydroxyisoiguesterin, pristimerin andisoiguesterol isolated from the roots of S.kraussiiby bioassay-guided fractionation have shownpotent cytotoxicity in HT-29 cells ( 27).
1.4.6 Antiinflammatory activity
The anti-inflammatory activity of S.oblonga rootbark powder was evaluated in male albino ratsusing carrageenan-induced rat paw oedema(acute inflammation) and cotton pellet granuloma(chronic inflammation) methods at a dose of1000 mg/kg was studied by Ismail andcoworkers. The increased acid and alkalinephosphatase activity and decreased serumalbumin in cotton pellet granulomatous rats werenormalized after treatment. The drug exerts theiractivity by antiproliferative, antioxidative andlysosomal membrane stabilization [66].
1.4.7 Antimalarial activity
Gessler and coworkers have studied forty-threedifferent plant species for antimalarial activity
against Plasmodium falciparum in vitro. The invitro testing revealed that 37% of the investigatedplants showed strong antimalarial activity withIC50 values below 10 g/ml. The four mostactive plants included Salacia madagascariensis,Cissampelos mucronata, Maytenus senegalensisand Zanthoxylum chalybeum [67].
Figueredo and coworkers have isolated28-nor-isoiguesterin-17-carbaldehyde, 17-(methoxycarbonyl)-28-nor-isoiguesterin, 28-hydroxyisoiguesterin, pristimerin andisoiguesterol from the roots of S.kraussii bybioassay-guided fractionation which showedantimalarial activity 30-50 fold greater than theextract itself [27].
1.4.8 Antiobese activity
Salacia is marketed as a Starch Blockersuggesting that it might help to reduce thebody weight. The effects of a mixture of theS.reticulata aqueous extract and cyclodextrin(SRCD) on the development of obesity wereexamined by Kishino and coworkers byevaluating the effects of SRCD on the elevationof plasma triacylglycerol levels induced by oraladministration of a high-fat (HF) liquid dietto male Sprague-Dawley rats. The plasmatriacylglycerol concentration was significantlylower in the SRCD treated rats than in thecontrol rats 4 h after HF diet administration.In an another study female C57BL/6 mice thatconsumed a solid HF diet containing 0.5%SRCD ad libitum for 8 week showed decreasein body weight and visceral fat mass than thosefed with HF diet . In addition, the energyefficiency and the plasma leptin andadiponectin concentrations were lower in themice that were administered SRCD than inthose fed the HF diet alone. The inhibitoryeffects of SRCD on HF diet–induced obesitymay be a ttributed to the inhibition ofcarbohydrate and lipid absorption from thesmall intestine [68].
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Yoshikawa and coworkers studied the antiobesityeffects of the hot water soluble extract (SRHW)from the roots of S.reticulata using obese ratmodels and an in vitro study. Body weight andperiuterine fat storage in female Zucker fatty rats(8-9 week old) were suppressed by oraladministration of SRHW (125 mg/kg) for 27days. Furthermore, SRHW inhibited porcinepancreatic lipase (PL), rat adipose tissue–derivedlipoprotein lipase (LPL) and glycerophosphatedehydrogenase (GPDH) activities with IC50 valueof 264 mg/L, 15 mg/L and 54 mg/L, respectively.(-)-Epigallocatechin and (-)-epicatechin-(4ß---8)-(-)-4'-O-methylepigallocatechin isolated from theroots of S.reticulata inhibited PL activity with IC50
of 88 and 68 mg/L, respectively. (-)-Epicatechin,3ß, 22ß-dihydroxyolean-12-en-29-oic acid andthe tannin fraction inhibited LPL activity with IC50
of 81, 89 and 35 mg/L. Only the tannin fractioninhibited GPDH activity with an IC50 of 6.8 mg/L. The polyphenolic compounds may be involvedin the antiobesity effects of SRHW in rats throughinhibition of fat metabolizing enzymes (PL, LPLand GPDH) and enhanced lipolysis [69].
Recent pharmacological reviews have shownthat Salacia roots modulate multiple targets forthe improvement of type 2 diabetes and obesity-associated hyperglycemia, dyslipidemia andrelated cardiovascular complications seen inhuman and rodents [70].
1.5. Toxicity studies
1.5.1 Antigenicity and phototoxicity reactions
The antigenicity and phototoxicity of watersoluble extract from S.reticulata (SRE) wereexamined by Shimoda and coworkers in guineapigs. In a study of active systemic anaphylaxisreaction, neither the oral administration group(64 or 320mg/kg, 5 times/week, 3 weeks) northe subcutaneous administration group (64mg/kg, 1 time/week, 3 weeks) exhibited anyanaphylactic reaction. In a phototoxicity study,oral admini-stration of SRE (320 mg/kg)
induced neither erythema nor edema. Theseresults suggest that SRE is not antigenic orphototoxic [71].
1.5.2 Toxicological and cytogenetic assessment
The toxicity of S.oblonga root extract wasevaluated in a sub chronic 90 days treatment inrats and was found to be safe as there was veryless chromosomal abberrations in cultured ratperipheral blood lymphocyte in vitro after 90days of treatment though the doses tested was10 times more than the intended dose for humans[72].
1.5.3 Genotoxicity
S.oblonga root extract did not show anygenotoxicity in number of tests like reversemutation assay, chromosomal abberration assay,mouse micronucleus assay as recommended byUS FDA with a very weak positive reproduciblechromosomal abberration of humanlymphocyte, though the dose used was 10 timesmore than the dose for human [73].
1.5.4 Contraindications and caution
A safety evaluation in animal models suggeststhat Salacia extract (both S.reticulata andS.oblonga) in doses 10 times what is suggestedfor humans for 14 days has no significantadverse reaction on blood chemistry,hematology or organ weights (74, 75, 76).Shimoda and coworkers showed no adverseeffect on food intake, body weight, bloodchemistry, organ weight or histopathologicalfindings on rats fed with S.reticulata extractat doses upto 1000 mg/Kg for 13 weeks ofcontinuous intake [77]. Animal study suggestsonly S.reticulata might adversely affectpregnancy with enhanced post-implantationlosses, pups with low birth weight. However,the root extract was non-teratogenic. It canbe concluded that the S. reticulata root extractcan be hazardous to successful pregnancy inwomen and should not be used in pregnancy
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1. Saldanha CJ. (1996) Flora of Karnataka,Oxford and IBH Publishing Co. Pvt Ltd:New Delhi; 92.
2. http : // envis.frlht.org.in/sreticulata.html
3. Indian Medicinal Plants - a Compendium of500 Species (1996), Orient Longman Ltd.:Hyderabad; 5: 47.
4. Lawerence GHM. (1951) Taxonomy of VascularPlants, Oxford and IBH Publishing Co. PvtLtd: New Delhi; 578.
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complicated by diabetes as there are reportsthat mugs made of S.reticulata woods areavailable to be used routinely by diabeticpatients to drink water [74].
1.5.5 Advers ereaction
Orally, Salacia can cause flatulence anddistention. Flatulence is more significant with a1000 mg dose compared to a 500 mg dose.Drinking Salacia tea can cause dyspepsia andloose stool [42].
1.5.6 Interaction with drugs
Salacia is thought to lower glucose levels.Combining Salacia with other antidiabetic drugs
(glimepiride, glyburide, insulin, pioglitazone,rosiglitazone) that also lower blood glucosemight have additive effect but increases the riskof hypoglycemia [78, 79].
1.5.7 Interaction with food, disease and othercondition
Not known.
1.5.8 Dosage / Administration
Oral: For Diabeties, Salacia tea has been usedthree times daily before meals. Salacia in dosesof 500 - 1000 mg in combination with mealshas been also used [79, 80].
38. Karunanayake EH, Welihinda J , Sirimanne SR,Sinnadorai G. (1984) J. Ethnopharmacol. 11(2): 223 – 231.
39. Serasinghe S, Serasinghe P,Yamazaki H,Nishiguchi K. et al. (1990) Phytotherapy Res.4 : 205-206.
40. Shimoda H, Kawamori S, Kawahara Y. (1998)Nippon Eiyo Shokuryo Gakkaishi Journalof the Japanese Society of Nutrition andFood Science. 51(5) : 279-287.
41. Tanimura C, Terada I, Hiramatu K, Ikeda T,Taniguchi M, et al. (2005) Yonago IgakuZasshi. 56: 85-93.
