Table Of ContentJournalofEthnopharmacology99(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-
Description: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