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JournalofEthnopharmacology99(2005)165–178 Review Antioxidant approach to disease management and the role of ‘Rasayana’ herbs of Ayurveda ∗ R. Govindarajan, M. Vijayakumar, P. Pushpangadan PharmacognosyandEthnopharmacologyDivision,NationalBotanicalResearchInstitute,Lucknow226001,India Received4November2004;receivedinrevisedform22February2005;accepted22February2005 Availableonline26April2005 Abstract Thediseasepreventiveandhealthpromotiveapproachof‘Ayurveda’,whichtakesintoconsiderationthewholebody,mindandspiritwhile dealingwiththemaintenanceofhealth,promotionofhealthandtreatingailmentsisholisticandfindsincreasingacceptabilityinmanyregions oftheworld.AncientAyurvedicphysicianshaddevelopedcertaindietaryandtherapeuticmeasurestoarrest/delayageingandrejuvenating wholefunctionaldynamicsofthebodysystem.Thisrevitalizationandrejuvenationisknownasthe‘Rasayanchikitsa’(rejuvenationtherapy). Traditionally,Rasayanadrugsareusedagainstaplethoraofseeminglydiversedisorderswithnopathophysiologicalconnectionsaccording tomodernmedicine.Though,thisgroupofplantsgenerallypossessesstrongantioxidantactivity,onlyafewhavebeeninvestigatedindetail. Overabout100disorderslikerheumatoidarthritis,hemorrhagicshock,CVSdisorders,cysticfibrosis,metabolicdisorders,neurodegenerative diseases,gastrointestinalulcerogenesisandAIDShavebeenreportedasreactiveoxygenspeciesmediated.Inthisreview,theroleoffree radicalsinthesediseaseshasbeenbrieflyreviewed.‘Rasayana’plantswithpotentantioxidantactivityhavebeenreviewedfortheirtraditional uses,andmechanismofantioxidantaction.Fifteensuchplantshavebeendealtwithindetailandsomemoreplantswithlessworkhavealso beenreviewedbriefly. ©2005ElsevierIrelandLtd.Allrightsreserved. Keywords: Rasayana;Antioxidant;Ayurveda;Panchkarma Contents 1. Introduction..................................................................................................... 166 2. ‘Rasayana’conceptof‘Ayurveda’................................................................................. 166 3. Freeradicalsandtheirroleindiseases.............................................................................. 167 3.1. Agingbiology............................................................................................. 167 3.2. Atherosclerosis............................................................................................ 168 3.3. Autoimmunediseases...................................................................................... 168 3.4. Cancer.................................................................................................... 168 3.5. Diabetes.................................................................................................. 168 3.6. Inflammation.............................................................................................. 168 3.7. Parkinson’sdisease......................................................................................... 169 3.8. Rhuematoidarthritis........................................................................................ 169 4. Antioxidantdefense.............................................................................................. 169 Abbreviations: CAT,catalase;DPPH,1,1-diphenyl-2-picrylhydrazyl;GSH,glutathione;GSH-px,glutathioneperoxidase;GSH-R,glutathionereductase; GST,glutathioneS-transferase;LDL,lowdensitylipoproteins;LPO,lipidperoxidation;MDA,malondialdehyde;RNS,reactivenitrogenspecies;ROI,reactive oxygenintermediates;ROS,reactiveoxygenspecies;SOD,superoxidedismutase;TBARS,thiobarbituricacidreactivesubstances ∗ Correspondingauthor.Tel.:+915222205848;fax:+915222205836. E-mailaddress:[email protected](P.Pushpangadan). 0378-8741/$–seefrontmatter©2005ElsevierIrelandLtd.Allrightsreserved. doi:10.1016/j.jep.2005.02.035 166 R.Govindarajanetal./JournalofEthnopharmacology99(2005)165–178 5. Rasayanaasantioxidants.......................................................................................... 169 5.1. Acoruscalamus............................................................................................ 170 5.2. Aloevera................................................................................................. 170 5.3. Andrographispaniculata.................................................................................... 170 5.4. Asparagusracemosus...................................................................................... 170 5.5. Azadirachtaindica......................................................................................... 171 5.6. Bacopamonnieri........................................................................................... 171 5.7. Desmodiumgangeticum.................................................................................... 171 5.8. Phyllanthusemblica........................................................................................ 171 5.9. Glycyrrhizaglabra......................................................................................... 172 5.10. Picrorhizakurroa......................................................................................... 172 5.11. Psoraleacorylifolia....................................................................................... 172 5.12. Semecarpusanacardium................................................................................... 172 5.13. Terminaliachebula........................................................................................ 173 5.14. Tinosporacordifolia...................................................................................... 173 5.15. Withaniasomnifera....................................................................................... 173 5.16. Miscellaneousplants...................................................................................... 174 6. Conclusion............................................................................................... 174 References............................................................................................... 175 1. Introduction body.Henceanymedicinethatimprovesthequalityof‘Rasa’ (‘Rasayana’)shouldstrengthenorpromotethehealthofall The health promotive, disease preventive and rejuvena- tissues of the body. ‘Rasayana’ drugs act inside the human tion approach available in the Indian systems of medicine body by modulating the neuro-endocrino-immune systems like ‘Ayurveda’ is gaining greater attention and popularity and have been found to be a rich source of antioxidants inmanyregionsoftheworld.Amajorityofthepresentday (Brahma and Debnath, 2003). These Rasayana plants are diseasesarereportedtobeduetotheshiftinthebalanceof saidtopossessthefollowingproperties:theypreventageing, thepro-oxidantandtheantioxidanthomeostaticphenomenon re-establish youth, strengthen life, brain power and prevent in the body. Pro-oxidant conditions dominate either due to diseases (Sharma, 1983; Ghanekar, 1981), all of which the increased generation of the free radicals caused by ex- imply that they increase the resistance of the body against cessive oxidative stress of the present day life, or due to anyonslaught. thepoorscavenging/quenchinginthebodycausedbydeple- ‘Rasayanachikitsa’isaspecializedsectionofAyurveda, tionofthedietaryantioxidants(Schulzetal.,2000;Dringen, which mainly deals with the preservation and promotion 2000).Thediseasepreventiveandhealthpromotiveapproach of health by revitalizing the metabolism and enhancing ofAyurveda,whichtakesintoconsiderationthewholebody, immunity. ‘Rasayana’ therapy is done for a particular mindandspiritwhiledealingwiththemaintenanceofhealth, period of time with strict regimen on diet and conduct. promotionofhealthandtreatingailments,isanholisticap- ‘Rasayana’ drugs are very rich in powerful antioxidants proachandfindsincreasingacceptabilityinmanyregionsof and are good hepatoprotective and immunomodulating theworld.TheancientAyurvedicphysiciansunderstoodthe agents.‘Rasayana’isnotadrugtherapy,butisaspecialized delicate cellular mechanisms of the body and the deterio- procedure practiced in the form of rejuvenation recipes, rationofthefunctionalefficiencyofthebodytissues.These dietaryregimenandspecialhealthpromotingrightconduct ancientAyurvedicmastershadthusdevelopedcertaindietary andbehavior,i.e.‘AcharaRasayana’.Shushruta(anancient andtherapeuticmeasurestoarrest/delayageingandrejuve- Ayurvedic surgeon) while defining ‘Rasayana’ therapy nating whole functional dynamics of the body organs. This says that it arrests ageing (‘Vayasthapam’), increase life revitalisationandrejuvenationisknownasthe‘Rasayanchik- span (‘Ayushkaram’), intelligence (‘Medha’) and strength itsa’(rejuvenationtherapy). (‘Bala’)andtherebyenableonetopreventdisease(Sharma, 1983).‘Rasayana’enhancesthefunctionsofthewholebody system.‘Rasayana’treatmentforrejuvenationisdoneafter 2. ‘Rasayana’conceptof‘Ayurveda’ thesystemisthoroughlycleansedby‘Panchakarma’therapy (Joshi, 1998). ‘Panchakarma’ is essentially a pretreatment Ayurvedicpharmacologyclassifiesmedicinalplantsinto equippingthebodytissuesfor‘Rasayana’therapy.Shushruta different groups according to their actions. One of these is observedthataperson,whosesystemisnotbeenpreviously the‘Rasayana’group.Theword‘Rasayana’literallymeans cleansed by proper purification remedies, cannot expect the path that ‘Rasa’ takes (‘Rasa’: plasma; Ayana: path). good results with ‘Rasayana’ treatment. ‘Panchakarma’ is It is believed, in Ayurveda that the qualities of the ‘Rasa- a method of purifying the body system by five methods dhatu’ influence the health of other dhatus (tissues) of the called ‘Vamana’ (emesis), ‘Virechana’ (purgation), ‘Vasti’ R.Govindarajanetal./JournalofEthnopharmacology99(2005)165–178 167 (enema),including‘Asthapana’(medicatedenema),‘Nasya’ burden in the body either due to environmental condition (nasal medication) and ‘Rakta moksha’ (blood letting) or produced within the body, it leads to oxidative stress, (Trikamji, 1994). According to the ‘Caraka Samhita’, one which may result in tissue injury and subsequent diseases oftheancienttreatisesof‘Ayurveda’,ifadiseaseisnotsub- (Finkel and Holbrook, 2000). Since free radicals play such jected to ‘Panchakarma’, the rejuvenation therapy may not an important role in the disease scenario of an individual, beeffective.‘Panchakarma’isadvisedfortreatingbroadcat- a thorough understanding of the various physiologically egoryofconditionslikearthritis,rheumatism,neurological, significant free radicals is of paramount importance before muscularskeletaldisordersandalsodegenerativeconditions the search of the radical scavengers or the antioxidant like infertility, menstrual problems, obesity, respiratory principles to treat the physiological disorders caused disorders, gastrointestinal disorders, etc. ‘Panchakarma’ bythem. may be administered with curative and corrective drugs Freeradicalsmaybedesignatedasmolecularsharksthat along with having powerful antioxidant activity (Devaraj, damage molecules in cell membranes, mitochondria (the 1980). cell’s energy plants), DNA (the cell’s intelligence) and are Therehasbeenaplentyofresearchontheplantsusedas veryunstable,tendtorobelectronsfromthemoleculesinthe Rasyanadrugsinordertoreasontheminthemoderncontext. immediatesurroundinginordertoreplacetheirownlosses. Puri(1970a,b,1971,1972)gaveanaccountoftheherbsused Reactive oxygen species (ROS) is a collective term, which •− • invarious‘Rasayana’preparationswhileUdupa(1973)stud- includesnotonlytheoxygenradicals(O ,and OH)but 2 iedtheeffectsof‘Rasayana’drugsonpsychosomaticstress. alsosomenon-radicalderivativesofoxygen.Theseinclude ‘Rasayana’drugshavebeenproventotreatepilepsy(Singh hydrogen peroxide (H O ), hypochlorous acid (HOCl) and 2 2 andMurhty,1989),convulsivedisorders(DiwediandSingh, ozone(O )(Bandhopadhyayetal.,1999). 3 1992)andtoreduceanxiety,apprehensionandkeepthemind Overabout100disorderslikerheumatoidarthritis,hem- calmandcool(Puri,2003).Plentyofstudyhasbeenunder- orrhagic shock, cardiovascular disorders, cystic fibrosis, takentoprovidescientificevidencetothe‘Rasayana’drugs metabolic disorders, neurodegenerative diseases, gastroin- asimmunomodulatorsandadaptogens.Wagner(1994)aftera testinalulcerogenesisandAIDShavebeenreportedasROS detailedstudyconcludedthat‘Rasayana’preparations,which mediated.SomespecificexamplesofROSmediateddiseases actbothasherbalimmunostimulantandadaptogens,regulate includeAlzheimersdisease,Parkinson’sdisease,Atheroscle- theimmunologicalandendocrinesystemswithrelativelylow rosis, Cancer, Down’s syndrome and ischemic reperfusion doses,withoutdamagingtheautoregulativefunctionsofthe injuryindifferenttissuesincludingheart,liver,brain,kidney organisms. ‘Rasayana’ drugs haven been reported to treat andgastrointestinaltract.TheroleplayedbyROSinstress- generalizedweakness(Jayarametal.,1993)andaffordpro- inducedgastriculcerandinflammatoryboweldiseaseshave tectionfromcyclophosphamide-inducedluekopenia(Kumar beenwellestablished,aswellastheirinvolvementinthepro- etal.,1994). cessofageing.Theroleofradicalsinvariousdiseasesisdealt indetail. 3. Freeradicalsandtheirroleindiseases 3.1. Agingbiology Free radicals are natural by-products of our own In the biological process of aging, the following metabolism. These are electrically charged molecules that cause–effect relationships are demonstrated: formation attack our cells, tearing through cellular membranes to of intra and intermolecular cross-linkings, as in the case react and create havoc with the nucleic acids, proteins, and of muscle cells aging. Modifications of immunological enzymespresentinthebody.Theseattacksbyfreeradicals, reactions, usually resulting in decrease of their activities. collectivelyknownasoxidativestress,arecapableofcausing Telomere shortening with decrease or interruption of cell cells to lose their structure, function and can eventually proliferation, which can mean an unbalance between cells destroythem.Theyarecontinuouslyproducedbyourbody’s lostandrepositionrates,culminationwithorganandsystem useofoxygensuchasinrespirationandsomecell-mediated failureanddeathoftheorganism.Celldamagesprovokedby immune functions. They are also generated through envi- freeradicalsarecommonduringaging;onceinthislifestep ronmental pollutants, cigarette smoke, automobile exhaust, cellsproducelessconcentrationsofantioxidantenzymeslike radiation,air-pollution,pesticides,etc.(LiandTrush,1994). superoxidedismutase(SOD),catalase(CAT),etc.Geneac- Normally there is a balance between the amount of free tivationwithinevitableaging-relatedphysiologicalchanges radicals generated in the body and the antioxidant defense (Harman, 1998; Ferrari, 2001). In healthy human cente- systemsthatscavenge/quenchthesefreeradicalspreventing narians, although both plasmatic and red blood cell-SOD them from causing deleterious effects in the body (Nose, were decreased (in concentration with the increasing levels 2000).Theantioxidantdefensesystemsinthebodycanonly since <60 years until 99 years), the remarkable increase of protect the body when the amount of the free radicals is plasmatic Vitamins A and E contribute the first indication withinthenormalphysiologicallevel.Butwhenthisbalance thatthesevitaminsarefavorabletolongevity(Mecoccietal., is shifted towards more of free radicals, increasing their 2000). 168 R.Govindarajanetal./JournalofEthnopharmacology99(2005)165–178 3.2. Atherosclerosis gestthattheycouldcontributetoallstagesofcarcinogenesis, however an excess of ROS/RNS can inhibit the cell prolif- Itisadiseaseofarteriescharacterizedbyalocalthicken- eration. Hence the net effect will depend upon the amount ingofthevesselwallthatdevelopsintheinnercoat(Tunica ofROS/RNSgeneratedandtheextentofantioxidantdefense intima).ItisnowbelievedandacceptedthatROS/RNSplay existing(Marnett,1987). animportantroleininitiationanddevelopmentofatheroscle- rosis.Thereareanumberofrolesbelievedtobeplayedbythe 3.5. Diabetes oxidantsinatherogenesis:firstly,activationofmacrophages or their monocyte precursors (Mitchinson and Ball, 1987). It has been postulated that the etiology of the compli- Secondly, normal macrophages possess some low density cations of diabetes involves oxidative stress perhaps as a lipoprotein(LDL)receptors.LDLboundtothesereceptorsis result of hypoglycemia (Hunt et al., 1990). Glucose itself takenupwithenhancedefficiency,sothatcholesterolrapidly and hyperglycemia-related increased protein glycosylation accumulates with in the macrophage and may convert it to areimportantsourcesoffreeradicals(WolffandDean,1987). a foam cell (Mitchinson and Ball, 1987). Thirdly, any lipid Elevatedglucosecausesslowbutsignificantnon-enzymatic peroxidespresentinLDLcouldconceivablycontributetothe glycosylationofproteinsindiabetes(Brownleeetal.,1984). initialendothelialcelldamagethatisthoughttostartoffthe Glucoseauto-oxidiseinthepresenceoftransitionmetalions whole process. Fourth, it has been suggested that products generatingoxygenfreeradicals,whichmakethemembrane formedinperoxidizedLDLsuchaslysophosphotidylcholine vulnerabletooxidativedamage.Asthediabetogenicaction (MitchinsonandBall,1987)mightactasachemotacticfac- canbepreventedbytheSOD,CAT,andotherhydroxylrad- torsforbloodmonocytes,encouragingtheirrecruitmentinto icalscavengerssuchasethanol,dimethylurea,thereisevi- anatheroscleroticlesion.Fifth,lowconcentrationofperox- dencetosuggestthattheincidenceofdiabetesinvolvessu- idesmightacceleratecycloxygenaseandlipoxygenasecatal- peroxide anion and hydroxyl radicals. In addition to these ysed reactions in endotheliym and in any platelets present enzymes,glutathionereductase(GSH-R)andglutathione-S- leadingtoenhancedformationofeicosanoids(Yokodaetal., transferanse(GST)provideGSHandhelptonutralizetoxic 1988). electrophiles, respectively. There are clear cut evidence to show the role of free radicals in diabetes and studies indi- 3.3. Autoimmunediseases catethattissueinjuryindiabetesmaybeduetofreeradicals (Grankvistetal.,1981).Thesignificanceofoxidativestress ItseemslikelythatROS,RNSandreleasedenzymessuch in the disease pathology is uncertain but is frequently pro- asproteasesplaysomeroleintissuedamageintheautoim- posed to be related to the hyperglycaemia. Other possible munediseases.Hencetherapyagainstthemmightproveben- sources include elevated plasma lipids leading to increased eficial.Example,urinaryexcretionofF isoprostanesisele- lipid oxidation and decreased levels of antioxidant defense 2 vatedinsclerodermapatientssuggestingincreasedlipidper- systems(BaynesandThorpe,1999). oxidation(LPO).Alsothelevelsofnitrateplusnitritetendto behigherinthepatientssufferingfromautoimmunediseases, 3.6. Inflammation • indicating more NO generation (Halliwell and Gutteridge, 1999). An inflammatory response implicates macrophages and neutrophils, which secrete a number of mediators (eicosi- 3.4. Cancer noids,oxidants,cytokineandlyticenzymes)responsiblefor initiation, progression and persistence of acute or chronic Most tumors form discrete masses but in the leukemias, state of inflammation (Lefkowitz et al., 1999). NO along •− thetumorcellsarespreadthroughthebonemarroworlym- withsuperoxide(O )andtheproductsoftheirinteraction 2 phoidtissuesandcirculateintheblood.DNAdamageplays initiates a wide range of toxic oxidative reactions causing averyimportantroleincarcinogenesisandanyagent,which tissue injury (Hogg, 1998). Likewise, the neutrophils iscapableofchemicallymodifyingDNAcouldbecarcino- too produce oxidants and release granular constituents genic.ROS/RNSfallintothiscategory.Hydroxylradicalat- comprising of lytic enzymes performing important role in tackuponDNAgeneratesawholeseriesofmodifiedpurine inflammatoryinjury(YoshikawaandNaito,2000).Reactive andpyrimidinebasesmanyofwhichareknowntobemuta- oxygen intermediates (ROI) are believed to be mediators • genic.Attackof OHupondeoxyribosealsoyieldsamulti- of inflammation and responsible for the pathogenesis of plicityofproducts.Itiswellknownthatincreasedproduction tissue destruction in rheumatoid arthritis (Valentao et al., ofROScancauseDNAdamageincells(Cerutti,1994).Ox- 2002). The role of ROS/RNS in inflammation is clearly idative damage to lipids and to proteins could also lead to demonstrated by the anti-inflammatroy effects of the an- mutagenic effects. One of effects of several tumor promot- tioxidants.Niricoxidesynthaseinhibitorsarealsoeffective ers including oxidative stress is to decrease the gap func- as anti-inflammatory agents in carrageenan-induced rat tionalcommunication,andfinallyROSmayalsobeinvolved paw odema method as SOD. These may be due to the •− •− in metastatin. Thus, the multiple effects of ROS/RNS sug- removal of O by SOD, so preventing O dependent 2 2 R.Govindarajanetal./JournalofEthnopharmacology99(2005)165–178 169 formationofafactorchemotacticfornutrophils(Milleretal., idizable substrate, that significantly delays or prevents oxi- 1992). dationsofthatsubstrate”.Thetermoxidizablesubstratein- cludes every type of molecule found in vivo. Antioxidant 3.7. Parkinson’sdisease defense include the antioxidant enzymes like SOD, CAT, GSH-px,etc,lowmolecularagentsanddietaryantioxidants TherehavebeenseveralreportsontheroleofROS/RNS (HalliwellandGutteridge,1999). inneurodegenertivediseases.Parkinson’sdiseaseusuallyap- pearsinthemiddletooldageoftenasarhythmictremorina footorhandespeciallywhenthelimbisatrest.Comparison 5. Rasayanaasantioxidants ofthebrainsofParkinson’sdiseasewiththatoftheneurologi- callynormalbrainsshowsseveralparametersconsistentwith Theconceptofdevelopingdrugsfromplantsusedinin- increasedoxidativestressanddefectivemitochondrialfunc- digenousmedicalsystemismucholder,whileinsomecases tion. Damaged mitochondria may generate more ROS than direct links between a local and biomedical use exists, in •− • − usualandROS/RNS(includingO , OH,ONOO )canin- othercasestherelationshipismuchmorecomplex(Heinrich 2 activatecomplexI.Henceitispossiblethatoxidativestress and Gibbons, 2001). Traditionally, ‘Rasayana’ drugs are andmitochindrialdefectsformaviciouscycle(Halliwelland usedagainstaplethoraofseeminglydiversedisorderswith Gutteridge,1999). no pathophysiological connections according to modern medicine.Lookingatthesediverseapplicationsadaptogenic 3.8. Rhuematoidarthritis agents from this group of ‘Rasayanas’ were identified by Regeetal.(1999).Ithasbeenreportedthatthe‘Rasayanas’ ROI produced by activated phagocytes in the in- arerejuvenators,nutritionalsupplementsandpossessstrong flamed joints have been implicated along with prostanoids, antioxidant activity. They also have antagonistic actions on leukotrienesandproteases,asmediatorsofinflammationand theoxidativestressorswhichgivingrisetotheformationof the pathogenesis of tissue destruction (Krane et al., 1990). different free radicals. Therefore, the therapeutic indication Many drugs commonly used in the day to day treatment of of these drugs can include the diseases relating to all the rheumatoid arthritis are believed to mediate their therapeu- above systems. Their antistress/adaptogenic actions have ticactionsbymultiplemechanisms,oneofthembeingsug- made them therapeutically far more important (Brahma gestedisareductionofoxidantdamageatsitesofinflamma- and Debnath, 2003). The strong antioxidant activity of tionbydrugseitheractingasROIscavengersorinhibitorsof any ‘Rasayana’ was found to be 1000 times more potent ROIproductionbyphagocytes(Aruoma,1993).Inhumans, than ascorbic acid, (cid:1)-tocopherol, and probucol (Sharma thereareintrinsicenzymaticandnon-enzymaticantioxidants et al., 1992). For example, oral administration of ‘Brahma detoxifyingmechanismsthathelptomaintainalowROIcon- rasayana’ (50mg/animal for 10 and 30 days) significantly centrationinthebody(Seiss,1991).Enzymaticmechanisms increasedtheliverantioxidantenzymessuchasSOD,CAT include SOD, which dismutates superoxide radicals, CAT alongwithtissueandserumlevelsofGSH.Thus,indicating andGSH-pxthatreduceH O towaterandmolecularoxy- that‘Brahmarasayana’couldamelioratetheoxidativedam- 2 2 gen(HalliwellandGutteridge,1999). ageproducedinthebodybyradiation(Rekhaetal.,2001). ‘Rasayana’ preparations also increased stem cell prolifera- tionandalsopreventedfreeradical-inducedinjuryproduced 4. Antioxidantdefense byradiation(Puri,2003).Hannaetal.(1994)alsoreported thepreventionofoxidantstressby‘StudentRasayana’. Itisevidentthroughthereactionsofoxygen,thatitistoxic; Sincefreeradicalsareimplicatedinanumberofphysio- stillonlytheaerobessurviveitspresence,primarilybecause logicaldisordersasdescribedaboveandwiththe‘Rasayana’ theyhaveevolvedaninbuiltantioxidantdefense.Antioxidant drugsofAyurvedausedinthetreatmentofdiversephysiolog- defensescomprise: icaldisorders,thereisastrongcasetobelievethat‘Rasayana’ drugsexerttheirtherapeuticactionsbytheirabilitytoscav- • Agentsthatcatalyticallyremovefreeradicalsandotherre- engefreeradicalsorbytheirantioxidantpotential.Therehas activespecieslikeSOD,CAT,peroxidaseandthiospecific beenareviewonsomeplantsofIndiantraditionalmedicine antioxidants. withantioxidantactivity(ScartezziniandSperoni,2000)and • Proteinsthatminimizetheavailabilityofperoxidasesuch areviewofimmunemodulatorsfrom‘Ayurveda’especiallyof asironions,copperionsandhaem. the‘Rasayana’drugs(AgarwalandSingh,1999).Butthereis • Proteinsthatprotectbiomoleculesagainstoxidativedam- notasinglereviewofthe‘Rasayana’drugsofthe‘Ayurveda’, ageexampleheatshockproteins. asantioxidants.SomeimportantplantslikeAlliumsativum, • LowmolecularmassagentsthatscavengeROSandRNS, Centella asiatica, Ocimum sanctum, Vitis vinifera and Zin- exampleGSH,ascorbicacid,tocopherol. giberofficinalehavebeenextensivelyreviewedintherecent The antioxidants may be defined as “any substance, when past. Important ‘Rasayana’ drugs are reviewed in detail for present at low concentrations compared with that of an ox- theirantioxidantactivityhere. 170 R.Govindarajanetal./JournalofEthnopharmacology99(2005)165–178 5.1. Acoruscalamus 5.3. Andrographispaniculata Acorus calamus Linn. (family: Acoraceae, Ayurvedic Andrographispaniculata(Burm.f.)Wallex.Nees(fam- name: ‘Vacha’) is a semi-aquatic, perennial, aromatic herb ily: Acanthaceae, Ayurvedic name: ‘Kalmegh’), which has withcreepingrhizomes.Sinceantiquity,calamusrhizomehas widespread distribution in India, was found to be a substi- beenusedformedicinalbaths,inincenseandtea.Itusedtra- tute for Swertia chirayta and it became popular as green ditionallyforflatulentcolicandchronicdyspepsia(Parotta, chirayta. In ‘Ayurveda’, the leaf juice is a household rem- 2001). In ‘Ayurveda’, the rhizome is used as an aromatic, edyforflatulence,lossofappetite,bowelcomplaintsofchil- stimulant,bitter,tonic,carminative,anti-spasmodic,emetic, dren,diarrhea,dysentery,dyspepsia,andgeneraldebility;it expectorant, emmenagogue, aphrodisiac, laxative, and di- ispreferablygivenwiththeadditionofaromatics.Decoction uretic(Kapoor,2001).Ithasalsobeenethnobotanicallyused orinfusionoftheleavesgivesgoodresultsinsluggishliver, inasthma,bronchitis,bodyache,cold,coughandinflamma- neuralgia,ingeneraldebility,inconvalescenceafterfevers, tion (Jain, 1991). The ethyl acetate extract of Acorus cala- andinadvancedstagesofdysentery(Kapoor,2001).Andro- muswasfoundtobepotentantioxidantbyinhibitionof1,1- graphis paniculata significantly decreased kidney TBARS diphenyl-2-picrylhydrazyl(DPPH)freeradical(Acunaetal., level (P<0.005) in normal rats along with increase in the 2002).Antioxidantactivity(invitro)byDPPHscavengingat activity of SOD and CAT, but had no significant effect on threedifferentconcentrations(0.2,0.1and0.01g/ml)showed GSH-pxactivityindiabeticratsshowingthatitpossessesan amaximumactivityof86.43%at0.2g/ml(Govindarajanet antihyperglycaemicproperty,andmayalsoreduceoxidative al.,2003a). stress in diabetic rats (Zhang and Tan, 2000). Administra- tionofAndrographispaniculatashowedprotectiveeffectin theactivityofSOD,CAT,GSH-px,GSH-Raswellthelevel 5.2. Aloevera ofGSHwithdecreasedactivityoflipidperoxidaseproving ithasantioxidantandhepatoprotectiveactivity(Trivediand Aloe vera Linn. (family: Aloaceae, Ayurvedic name: Rawal,2001).‘Kalmegh’treatedgroupshowedasignificant ‘Kumari’)iscommonlyknownasaloe.In‘Ayurveda’,dried decrease in activity of LDL and MDA formation and CAT, juice of Aloe vera is cathartic and given in constipation. GSH-pxandGSH-Rshowedsignificantincreasesonlyatthe TheexpressedjuiceofAloeveraintheformofanointment higherdoseintheliver(Singhetal.,2001). in vaseline has been found to hasten healing of wounds of thermal burns and radiation injury. It has been found that 5.4. Asparagusracemosus aloecompoundisveryusefulincasesoffunctionalsterility anddisturbedmenstrualfunction.Itisafavoriteremedyfor Asparagus racemosus Willd. (family: Asparagaceae, intestinalwormsinchildren.TheAyurvedicdrugknownas Ayurvedic name: ‘Shatavari’), is a tall climber under-shrub ‘Kumariasava’isusefulingeneraldebility,cough,asthma, found all over India. Almost all parts of this plant are used piles,epilepsyandcolic(Kapoor,2001).8-C-(cid:2)-d-[2-O-(E)- bytheIndiantraditionalsystemofmedicine(‘Ayurveda’and Coumaroyl]glucopyranosyl-2-[2-hydroxy]-propyl-7-metho- ‘Unani’)forthetreatmentofvariousailmentsinhumanbe- xy-5-methylchromone, a potent antioxidative compound ings.Inparticular,therootsareusedindysentery,diarrhoea, has been isolated from a methanolic extract of Aloe (Lee tuberculosis,leprosy,skindiseases,epilepsy,inflammations, etal.,2000).Aloesinderivativesisorabaichromonetogether andasanexpectorant(Jain,1991;Nadkarni,1976).Theaque- withferuloylaloesinandp-coumaroylaloesinfromAloevera ousextractsofbothfreshanddriedrootswerefoundtohave showedpotentDPPHradicalandsuperoxideanionscaveng- amylase and lipase activities (Kapoor, 2001). The antioxi- ingactivities.Electronspinresonance(ESR)usingthespin dant effect of an active fraction consisting of polysaccha- trappingmethodsuggestedthatthepotentsuperoxideanion rides (termed as P3) fraction was more pronounced against scavengingactivityofisorabaichromonemayhavebeendue LPO, as assessed by TBARS formation, while that of the toitscaffeoylgroup(Yagietal.,2002).Polysaccharidesand crude extract was more effective in inhibiting protein oxi- flavonoids fractions along with aloe extracts showed sig- dation. Both the crude extract and P3 fraction also partly nificantantioxidantactivity(Huetal.,2003).Experimental protectsagainstradiation-inducedlossofproteinthiolsand investigationsperformedafter3,7and10daysexposureto inactivation of SOD. The inhibitory effects of these active radiation showed that Aloe vera treatment has significantly principles, at the concentration of 10(cid:3)g/ml, are compara- minimized the radiation-induced increase in the amount of bletothatoftheestablishedantioxidantsGSHandascorbic malondialdehyde (MDA) in liver, lungs, and kidney tissues acid(Kamatetal.,2000).TheAsparagusracemosusextract ofirradiatedrats.SignificantameliorationinSODandCAT supplemented mice displayed an improvement in GSH-px activitieswasobserved(Saadaetal.,2003).Thecombination activityandGSHcontentandreductioninmembranalLPO of extracts of Withania somnifera and Aloe vera was more (Parihar and Hemnani, 2003). Antioxidant compound race- effective in reducing oxidative damage in brain regions mofuranwasisolatedfromAsparagusracemosus,whichre- than the supplementation of single plant extract (Parihar et vealed activity against DPPH with IC value of 130(cid:3)M 50 al.,2004). (Wiboonpun et al., 2004). Asparagus racemosus (100 and R.Govindarajanetal./JournalofEthnopharmacology99(2005)165–178 171 250mg/kg body weight) for 3 weeks significantly reversed CAT and GSH-px activities (Bhattacharya et al., 2000a). It antioxidantenzymeslikeSODandCATinliverandkidneyin showed a dose-dependent free radical scavenging capacity diabeticrats.Itpossessesmoderateantidiabeticactivity,but andaprotectiveeffectonDNAcleavageandwasconfirmed itexhibitspotentantioxidantpotentialindiabeticconditions by a significant protective effect on H O -induced cytoxic- 2 2 (Govindarajanetal.,2004). ityandDNAdamageinhumannon-immortalizedfibroblasts (Russoetal.,2003).TreatmentwithBacopamonnieriextract 5.5. Azadirachtaindica significantlyincreasedtheantioxidantenzymessuchasCAT, SOD,GSH-pxandthelevelsofGSH,inhibitedlipidperox- AzadirachtaindicaA.Juss.(family:Meliaceae,Ayurvedic idationandreducedthetumormarkers(Rohinietal.,2004). name: ‘Nimba’) is commonly known as neem. It is very useful in blood disorders, eye diseases, intermittent fever, 5.7. Desmodiumgangeticum aswellaspersistentlowfever.Oilisveryusefulinleprosy, skin diseases, ulcers, and wounds. The bark contains a Desmodium gangeticum (L.) DC. (family: Fabaceae, resinous bitter principle and is usually prescribed in the Ayurvedicname:‘Shalparni’)isasmallshruboftropicalre- form of a tincture or an infusion. It is also regarded as gionwhichhasbeenusedinIndiansystemofmedicineasa beneficialinmalarialfever(Kapoor,2001).Theantioxidant bittertonic,febrifuge,digestive,anticatarrhal,antiemetic,in propertyofAzadirachtaindicahasbeenreported(Raoetal., inflammatory conditions of chest and various other inflam- 1998).Neemleafextracts(100,200and400mg/kg)showed matory conditions (Chopra et al., 1956). Though the roots its chemoprotective effects on potent gastric carcinogen oftheplantareoneoftheingredientsofpopularAyurvedic (cid:4) N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-induced drug–Dashmoola,apotentrejuvenatingformulationusedin oxidative stress by decreasing LPO and enhancing the an- ‘Ayurveda’, the aerial parts of this plant are mostly used as tioxidantenzymeslikeSOD,CAT,GSH-pxandGSTinmale a substitute in Dashmoola. Desmodium gangeticum extract rats (Subapriya et al., 2003). Ethanolic neem leaf extract haspotentantioxidantactivity,achievedbyscavengingabil- exerts protective effects against MNNG-induced genotox- ities observed against DPPH, nitric oxide, ferryl-bipyridyl icity and oxidative stress by augmenting host antioxidant and hypochlorous acid and LPO activity (Govindarajan et defence mechanisms (Subapriya et al., 2004). Azadirachta al.,2003b). indicaextractdemonstratedanticanceractivitybyincreasing the distribution of antioxidant elements and GST activity 5.8. Phyllanthusemblica to protect cells in preneoplastic nodules in cancer treated groups (Hanachi et al., 2004). Modulatory effects of garlic PhyllanthusemblicaL.(family:Euphorbiaceae,Ayurve- and neem leaf on hepatic and blood oxidant–antioxidant dic name: ‘Amalaki’) is considered best among ‘Rasayana’ statusmayplayakeyroleinpreventingcancerdevelopment so called ‘Acharasayana’ (Puri, 2003). In ‘Ayurveda’, fresh atextrahepaticsites(Arivazhaganetal.,2004). fruitisusedininflammationofthelungsandoftheeyesas acollyrium.Theseedsareusedinthetreatmentofasthma, 5.6. Bacopamonnieri bronchitis,andbiloiousness.Thedriedfruitisusefulinhem- orrhage, diarrhea, and dysentery. In combination with iron Bacopamonnieri(Linn.)Penn.(family:Scrophulariaceae, it is used as a remedy for anemia, jaundice, and dyspepsia. Ayurvedic name: Brahmi). Leaves and stalks are very use- Acutebacillarydysenterymaybecuredbydrinkingasyrup ful in the stoppage of urine, which is accompanied by ob- ofamlawithlemonjuice.‘Chyvanaprash’,apopularprepara- stinate costiveness. A poultice made of the boiled plant is tioncontainingEmblicaofficinalis,isveryusefulinanemia, placed on the chest in acute bronchitis and other coughs of asthma,inflammationsofthelungsandeyediseases(Kapoor, children.Leavesalsogivesatisfactoryresultsincasesofas- 2001).TheactivetannoidsofEmblicaofficinalisconsisting thenia, nervous breakdown, and other low adynamic con- of emblicanin A (37%), emblicanin B (33%), punigluconin ditions. It is also given in combination with ‘Ghrita’ (ani- (12%)andpedunculagin(14%),administeredinthedosesof malfat),awell-knownAyurvedicmedicine(brahmighrita) 5and10mg/kg,i.p.,anddeprenyl(2mg/kg,i.p.),inducedan in cases of hysteria and epilepsy. It is also useful in insan- increase in both frontal cortical and striatal SOD, CAT and ity, neurasthenia, aphonia and hoarseness (Kapoor, 2001). GSH-pxactivity,withconcomitantdecreaseinLPOinbrain Bacopa monnieri, is clinically used for memory enhanc- areaswhenadministeredoncedailyfor7days(Bhattacharya ing, epilepsy, insomnia and as mild sedative. It protected etal.,1999).FreshjuiceofEmblicafruits(50and100mg/kg the autooxidation and FeSO -induced oxidation of GSH bodyweight)givenorallytwicedailyfor14daysincreased 4 on lower doses 100(cid:3)g/ml and below, but on higher con- theactivitiesofcardiacSOD,CATandGSH-px,withacon- centrations it enhanced the rate of oxidation (Tripathi et comitant decrease of LPO in Ischemia-reperfusion-induced al., 1996). Extract of Bacopa monnieri was assessed on rat rats(Bhattacharyaetal.,2002).Emblicaofficinalisinhibited brain frontal cortical, striatal and hippocampal SOD, CAT LPOinducedwithFe(2+)/ascorbatealongwithinhibitionof and GSH-px activities, following administration for 7, 14 hydoxylandsuperoxideradical(SabuandKuttan,2002).A or 21 days which induced a dose-related increase in SOD, standardizedextractofEmblicaofficinaliswasfoundtohave 172 R.Govindarajanetal./JournalofEthnopharmacology99(2005)165–178 along-lastingandbroad-spectrumantioxidantactivity,thus pounddecoctionofitsroot,liquorice,raisins,andneembark showing that Emblica is suitable for use in anti-aging, sun- isverycurative;indyspepsiawithseverepains,thepowderof screen and general purpose skin care products (Chaudhuri, ‘kutki’,Acoruscalamus,chebulicmyrobalan,andplumbago 2002). Administration of Emblica tannoids (10 and 20mg, rootinequalpartsisgivenindosesof28mlwithcow’surine. po) for 21 days, concomitant with the stress procedure, in- Inclinicalstudiesonpatientsofinfectivehepatitiswithjaun- duced a dose-related alteration in the stress effects. Thus, dice,Picrorhizakurroawasreportedtohaveledtoarapidfall antistress‘Rasayana’activityofEmblicaofficinalismaybe, in serum bilirubin levels toward normal range and quicker atleastpartlyduetoitstendencytonormalizestress-induced clinicalrecoverywithnountowardeffects.Picrorhizakurroa perturbations in oxidative free radical scavenging activity led to beneficial results in the management of bronchial (Bhattacharya et al., 2000b). The presence of ‘Amlaki’ re- asthma. The drug is also reported to produce marked re- sulted in an enhanced cell survival, decreased free radical ductioninserumcholesterolandcoagulationtime(Kapoor, productionandhigherantioxidantlevels(Sairametal.,2003). 2001). Picroliv, the active principle of Picrorhiza kurrooa, Emblicaofficinaliscausesmyocardialadaptationandprotects anditsmaincomponentswhichareamixtureoftheiridoid againstoxidativestressinischemic-reperfusioninjuryinrats glycosides,picroside-Iandkutkosidepossesstheproperties (Rajaketal.,2004). ofantioxidantswhichappeartobemediatedthroughactivity like that of SOD, metal ion chelation and xanthine oxidase 5.9. Glycyrrhizaglabra inhibition (Chander et al., 1992). The extract (1mg/ml) showed marked protection (up to 66.68%) against peroxi- Glycyrrhiza glabra Linn. (family: Fabaceae, Ayurvedic dationofliverphospholipidsbesides,reducedGSHshowed name: ‘Yashtimadhu’) is commonly known as licorice. In veryencouragingactivity.Theextractalsoexhibitedsignif- Ayurveda, root in infusion, decoction, or extract is used icant free radical scavenging activity (Govindarajan et al., as a demulcent in inflammatory or irritable conditions of 2003c). the bronchial tubes, bowels, and catarrh of the genitouri- narypassage,suchascough,hoarseness,sorethroat,asthma 5.11. Psoraleacorylifolia and dysuria (Kapoor, 2001). Seven constituents, with an- tioxidant capacity were isolated from Glycyrrhiza glabra Psoralea corylifolia Linn. (family: Leguminoceae, which include isoflavans hispaglabridin A, hispaglabridin Ayurvedic name: ‘Vakuchi’). In Ayurveda, seed powder (cid:4) B, glabridin, and 4-O-methylglabridin, the two chalcones, is used in leprosy and leukoderma internally; and is also isoprenylchalcone derivative and isoliquiritigenin, and the applied in the form of paste or ointment externally. As a isoflavone, formononetin (Vaya et al., 1997). The effect of laxative it is particularly used in bilious disorders (Kapoor, the consumption of glabridin, an isoflavan isolated from 2001). A meroterpene and four flavonoids bakuchiol, Glycyrrhiza glabra root, on the susceptibility of low den- bavachinin, bavachin, isobavachin and isobavachalcone sitylipoproteintooxidationwasmoderateinatherosclerotic were isolated from the seeds of Psoralea corylifolia as apolipoproteinEdeficientmice(Belinkyetal.,1998).Rab- antioxidativecomponents.Theyshowedbroadantioxidative bits were treated (orally) with a preparation of Glycyrrhiza activities in rat liver microsomes and mitochondria. They glabrafor30daysandinparallelwereexposedtovibration inhibited NADPH-, ascorbate-, t-BuOH- and CCl -induced 4 stress(30days).ThelicoricepreparationreducedCATactiv- LPOinmicrosomes.TheyalsopreventedNADH-dependent ityintheperipheralbloodandincreasedanimalresistanceto and ascorbate-induced mitochondrial LPO (Haraguchi et vibrationstress(Oganesyan,2002).Fivenewprenylateddi- al., 2002). Psoralea corylifolia showed higher activity in hydrostilbenes, (cid:1),(cid:1)(cid:4)-dihydro-3,5,4(cid:4)-trihydroxy-4,5(cid:4)-diisop- phospholipid peroxidation inhibition (Tang et al., 2004). entenylstilbene,(cid:1),(cid:1)(cid:4)-dihydro-3,5,3(cid:4),4(cid:4)-tetrahydroxy-4,5(cid:4)-di- Bakuchiol, corylifolin, corylin and psoralidin isolated from isopentenylstilbene, (cid:1),(cid:1)(cid:4)-dihydro-3,5,4(cid:4)-trihydroxy-5(cid:4)-isop- Psoralea corylifolia had strong antioxidant activities, and entenylstilbene,(cid:1),(cid:1)(cid:4)-dihydro-3,5,3(cid:4)-trihydroxy-4(cid:4)-methoxy- especiallypsoralidinhadstrongerantioxidantpropertythan 5(cid:4)-isopentenylstilbene, and (cid:1),(cid:1)(cid:4)-dihydro-3,5,3(cid:4),4(cid:4)-tetrahyd- butylatedhydroxytoluene(Jiangningaetal.,2005). (cid:4) roxy-5-isopentenyl stilbene with antioxidant activity were isolated(Biondietal.,2003). 5.12. Semecarpusanacardium 5.10. Picrorhizakurroa SemecarpusanacardiumLinn.f.(family:Anacardiaceae, Ayurvedicname:Bhalatak)iscommonlyknownasmarking Picrorhiza kurroa Royle ex Benth (family: Scrophulari- nut.In‘Ayurveda’,thejuiceoftheshellofthenutisapower- aceae,Ayurvedicname:‘Kutki’),isfoundintheHimalayan fulescharotic;itisgiveninsmalldoseswithsomeblandoil region growing at an altitude of 3000–5000m. It is a well- orbutterinleprousandscrofulousaffections,syphilis,skin knownherbinAyurvedicsystemofmedicineandhastradi- diseases,epilepsy,nervousdebility,neuralgia,asthma,dys- tionallybeenusedtotreatdisordersoftheliverandupperres- pepsia,andpiles.Thebruisednutisusedasanabortifacient piratorytract,reducefeverandtreatdyspepsia,chronicdisor- by placing it in the mouth of the uterus; also given as ver- dersandscorpionsting(Jain,1991).Inbiliousfever,acom- mifuge.Equalpartsofmarkingnutandchebulicmyrobalams R.Govindarajanetal./JournalofEthnopharmacology99(2005)165–178 173 andsesamumseedsaremadeintoaconfection(‘Kshirpak’) starchobtainedfromtherootsandstemsoftheplantisuseful andadministeredindosesof3–4gm.Itisusedwithadvan- indiarrheaanddysentery,itisalsoanutrient.Thefreshplant tage in simple chromic enlargement of the spleen without is more efficacious than the dried plant. Its watery extract, anyhepaticcomplicationorfever.Itisusedinmanyneurotic, knownasIndianquinine,isveryeffectiveinfeversduetocold cardiactroubles;therateoftheheartbeatisusuallyincreased or indigestion; the plant is commonly used in rheumatism, under its influence. It is also useful in cases of pneumonia urinary diseases, dyspepsia, general debility, syphilis, skin (Kapoor,2001).AdministrationofSemecarpusanacardium diseases,bronchitis,spermatorrhea,andimpotence(Kapoor, nutextract150mg/kgbodyweightfor14daysonadjuvant 2001).As‘Rasayana’,juiceisgivenwithhoneyorrawsugar arthritis brings back the altered antioxidant defense com- (Puri,2003).ExtractofTinosporacordifoliahasbeenshown ponents evidenced by the increased level of non-enzymatic to inhibit the LPO and superoxide and hydroxyl radicals in antioxidants (GSH, Vitamin E, Vitamin C) and enzymatic vitro(MathewandKuttan,1997).Oraladministrationofan antioxidants(CATandGSH-pxexceptSOD)tonearnormal aqueousTinosporacordifoliarootextract(2.5and5.0g/kg) levels(Vijayalakshmietal.,1997).Semecarpusanacardium for 6 weeks resulted in a decrease in the levels of plasma nut extract administration induces the in vivo antioxidant TBARS,ceruloplasminand(cid:1)-tocopherolinalloxandiabetic defensesysteminaflatoxinB1mediatedhepatocellularcar- rats. The root extract also causes an increase in the levels cinomawithmarkedincreaseinantioxidantlevelsandadra- of GSH and vitamin C in alloxan diabetes rats (Prince and maticelevationincytochromeP450content(Premalathaand Menon,1999).Oraladministrationof2.5gand5.0g/kgbody Sachdanandam,1999).Alcoholicextractofpericarpshowed weight of the aqueous extract of the roots for 6 weeks re- significantprotectionagainstFeSO -inducedlipidperoxida- sultedinasignificantreductioninTBARSandanincreasein 4 tion,ascomparedwithwholenativenutandseeds.Mecha- reducedGSH,CATandSODinalloxandiabeticrats(Prince nismofactionmaybethroughmetalchelationoractivation andMenon,2001,Princeetal.,2004).Thearabinogalactan of endogenous antioxidant enzymes (Tripathi and Singh, polysaccharide isolated from Tinospora cordifolia showed 2001). goodprotectionagainstiron-mediatedLPOofratbrainho- mogenateasrevealedbytheTBARSandlipidhydroperoxide 5.13. Terminaliachebula assays and high reactivity towards DPPH, superoxide radi- cals and the most damaging of radicals, the hydroxyl rad- Terminalia chebula Retz. (family: Combretaceae, ical (Subramanian et al., 2002). Aqueous extract inhibited Ayurvedicname:‘Haritaki’).In‘Ayurveda’,myrobalansare theformationofferryl–bipiridylcomplexbychelatingFe2+ used in fevers, cough, asthma, urinary diseases, piles and ions in a dose dependent manner. It also inhibited ferrous worms. It is also useful in chronic diarrhea and dysentery, sulphate mediated LPO in a dose-dependent manner (Goel flatulence, vomiting, colic and enlarged spleen and liver. etal.,2002).Tinosporacordifoliawaseffectiveinelevating Chebulic myrobalans are extensively used in combination the GSH levels, expression of the gamma-glutamylcysteine with belleric and embolic myrobalans under the name ligaseandCu–ZnSODgenesandalsoexhibitedstrongfree of ‘Triphala’ and also as adjuncts to other medicines in radicalscavengingpropertiesagainstROSandRNSasstud- numerous diseases (Kapoor, 2001). As a ‘Rasayana’, 3g iedbyelectronparamagneticresonancespectroscopy(Rawal of ‘Haritaki’ is used in the morning in empty stomach for etal.,2004). body strengthening and anti-aging (Puri, 2003). Terminalia chebula (fruits, brown) were stronger antioxidants than 5.15. Withaniasomnifera alpha-tocopherol,whileTerminaliachebula(fruitcoat)and Terminalia chebula (fruits, black) were weaker antioxidant Withania somnifera Dunal (family: Solanaceae, extractsthanalpha-tocopherolandbutylatedhydroxytoluene Ayurvedic name: ‘Ashwagandha’) has been in use for ininhibitionofLPOinvitro(Saleemetal.,2001).Emblica morethan2500years.Therootsoftheplantarecategorised officinalis inhibited LPO induced with Fe(2+)/ascorbate as ‘Rasayanas’, a group of plant-derived drugs that are along with inhibition of hydoxyl radical, and superoxide reputed to promote health and longevity by augmenting scavenging (Sabu and Kuttan, 2002). Terminalia chebula defense against disease, arresting the aging process, revi- showed maximum inhibition in the TBARS formation, talising the body in debilitated conditions, increasing the restoreantioxidantenzymeSODfromtheradiation-induced capability of the individual to resist adverse environmental damage (Naik et al., 2003). Terminalia chebula exhibited factors and creating a sense of mental well-being (Weiner antioxidant activity at different magnitudes of potency for and Weiner, 1994). In ‘Ayurveda’, it is used as nerve tonic, anti-LPO,anti-superoxideradicalformationandfreeradical aphrodosiac, sedative, antirhuematism, for the treatment of scavengingactivities(Chengetal.,2003). constipation. It relieves inflammation, pain, backache and it stimulates sexual impulses and increases sperm count. 5.14. Tinosporacordifolia It is considered as a ‘Rasayana’ for strength, vigor and rejuvenation. Powders of Withania (100g) and Tinospora Tinospora cordifolia (Willd.) Miers. (family: Menisper- (50g) and Tinospora starch (10g) are mixed and half a maceae, Ayurvedic name: ‘Guduchi’). In ‘Ayurveda’, the spoon of this powder is taken with half teaspoons of ghee 174 R.Govindarajanetal./JournalofEthnopharmacology99(2005)165–178 and two teaspoons of honey (Puri, 2003). Root is used as plexandLPO(Vijayakumaretal.,2005).Alcoholicextractof anapplicationinobstinateulcersandrheumaticswelling.It theseedsofMucunapruriens(Linn.)DC.hasanantilipidper- infuses fresh energy and vigor in a system worn out owing oxidationproperty,whichismediatedthroughtheremovalof toanyconstitutionaldiseaselikesyphilis,andinrheumatic superoxides and hydroxyl radicals (Tripathi and Upadhyay, fever.Powderedrootisveryusefulwithequalpartsofghee 2002). The antioxidant components of Piper species, viz., andhoneyforimpotenceorseminaldebility.Asnutrientand Piper cubeba, green pepper, Piper brachystachyum, Piper healthrestorativetothepregnantandoldpeople,adecoction longumandPipernigrumconstituteaveryefficientsystem of the root is recommended (Kapoor, 2001). Thirty days inscavengingawidevarietyofreactiveoxygenspecies.An- treatment Withania somnifera root produced a significant tioxidantpotentialofPiperspecieswasfurtherconfirmedby decreaseinLPO,andanincreaseinbothSODandCATthus theirabilitytocurtailinvitroLPObyaround30–50%with indicating that Ashwagandha root powder possesses free concomitantincreaseinGSHcontent(KarthikeyanandRani, radical scavenging activity (Panda and Kar, 1997). Active 2003). In ferric reducing/antioxidant power (FRAP)/DPPH glycowithanolides,sitoindosidesVII-XandwithaferinAof assays, boiled ethanolic extracts of Plumbago zeylanica L. Withania somnifera (10 and 20mg/kg, i.p.), administered were the most effective, while in the ABTS assay boiled once daily for 21 days, induced a dose-related increase aqueousextractswerethemostefficient.Theseextractsalso in SOD, CAT and GSH-px activity in frontal cortex and significantly inhibited LPO induced by cumene hydroper- striatum, which was statistically significant on days 14 and oxide, ascorbate-Fe(2+) and peroxynitrite. Thus, Extracts 21 (Bhattacharya et al., 1997). Administration of Withania of Plumbago zeylanica and its active ingredient plumbagin somnifera in the doses of 0.7 and 1.4g/kg body weight per have significant antioxidant abilities that may possibly ex- dayalongwithequivalentdosesofleadacetatefor20days plain some of the reported therapeutic effects (Tilak et al., significantly decreased LPO and increased the activities of 2004).ABTSassayshowedthattheethanolicextractofSida antioxidant enzymes, viz., SOD and CAT, thus retaining cordifolia L. was found to be most potent along with rela- normal peroxidative status of the tissues (Chaurasia et al., tive antioxidant capacity for the water infusions and potent 2000).Withaniasomniferaglycowithanolides,administered inhibitionofLPO.EvolvulusalsinoidesandCynodondacty- orally 1h prior to the stress procedure for 21 days, in the lon were also found to be moderately active (Auddy et al., dosesof10,20and50mg/kg,inducedadose-relatedreversal 2003). of the stress effects. Withania somnifera glycowithanolides tendedtonormalisetheaugmentedSODandLPOactivities and enhanced the activities of CAT and GSH-px indicating 6. Conclusion that, at least part of chronic stress-induced pathology may be due to oxidative stress, lending support to the clinical Ayurvedic concept of ‘Rasayana’ seems not only to em- useoftheplantasanantistressadaptogen(Bhattacharyaet body the principal aspects of new hypothesis centered on a al., 2001). Treatment with Withania somnifera successfully immuno-endocrinepsychoneuroaxisbutalsotogobeyond attenuated GSH-px activity and inhibited LPO in a dose itbyencompassingtheentirehumansystemwithitsdiverse dependent manner. Withania somnifera inhibited both the andcomplicatedimmunoendocrinepathway(Handa,1993). LPO and protein oxidative modification induced by copper ItwaswellknowntoAyurvedicphysiciansthatthedelicate (Guptaetal.,2003).ThecombinationofextractsofWithania cellular machinery of the body suffers from trauma, result- somnifera and Aloe vera was more effective in reducing ing in wear and tear on different body structures and the oxidativedamageinbrainregionsthanthesupplementation deteriorationofthefunctionalcapacity.Forthis,procedures of single plant extract (Parihar et al., 2004). Given the of revitalization and rejuvenation (Rasayana therapy) were increasingrecognitionthatchronicstress,particularlywhen adoptedtoincreasethepowerofresistancetodisease,these the individual is unable to cope with the stressor, may proceduresretardedadvancementofagingalso. underlie the increasing incidence of stress-related physical Thedatainthereviewoftheplantsfortheirantioxidant andmentaldisorders,thereisneedforaneffectiveantistress activitysofarprovethat‘Rasayana’plantscouldexertamore adaptogen. The answer probably lies in the ‘Ayurvedic’ globalandnonspecificantioxidanteffect.However,itisalso ‘Rasayana’, the most promising of which is Withania evidentthateachplantisuniqueinitsactionandmaybeex- somnifera(WeinerandWeiner,1994). erting specific protective effects on specific organ/enzymes morethanothers.Thereisalsotremendousamountofreports 5.16. Miscellaneousplants oftheplantsasantioxidantsundervariousdiseaseconditions like diabetes, cancer, atherosclerosis and arthritis, proving Curculigo orchioides Gaertn. had high antioxidant ac- that the mechanism involved may be in curing these dis- (cid:4) tivity in 2,2-azinobis[3-ethylbenzothiazoline-6-sulfonate] easesmaybeofantioxidants.Fromthereview,itisevident (ABTS) assay (Tang et al., 2004). Hygrophila auriculata that most of the ‘Rasayana’ plants possess potent antioxi- (Schum.) Hiene. extract showed good radical scavenging dantactivity.Butstillthereislacunaintheexistingknowl- activity against DPPH with moderate scavenging activity edge. Firstly, some ‘Rasayana’ group of plants like Alpinia againstNitricoxide,hydroxylradical,ferrylbipyridylcom- galanga, Argyreia speciosa, Boerhaavia diffusa, Convolvu-

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Traditionally, Rasayana drugs are used against a plethora of seemingly diverse disorders with no pathophysiological connections according to modern Keywords: Rasayana; Antioxidant; Ayurveda; Panchkarma. Contents. 1. 'Rasayana chikitsa' is a specialized section of Ayurveda, which mainly
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