Ashwagandha(withania somnifera)

n Ayurveda, withania is widely claimed to have potent aphrodisiac, sedative, rejuvenative and life prolonging properties. It is also used as a general energy-enhancing tonic known as Medharasayana, which means 'that which promotes learning and a good memory' and in geriatric problems.

1. (Withania Somnifera)
Ashwagandha (Withania Somnifera)

2. Aswagandha In Ayurveda
2
InAyurveda,Withaniaiswidelyclaimedtohavepotentaphrodisiac,sedative,rejuvenativeand
lifeprolongingproperties.Itisalsousedasageneralenergy-enhancingtonicknownas
Medharasayana,whichmeans‘thatwhichpromoteslearningandagoodmemory’andin
geriatricproblems.
Theplantwastraditionallyusedtopromoteyouthfulvigor,endurance,strength,andhealth,
nurturingthetimeelementsofthebodyandincreasingtheproductionroductionofvital
fluids,musclefat,blood,lymph,semenandcells.
Thesimilaritybetweentheserestorativepropertiesandthoseofginsengrootshasledto
AshwagandharootsbeingcalledIndianginseng.
Italsohelpscounteractchronicfatigue,weakness,dehydration,boneweakness,looseteeth,
thirst,impotency,prematureageing,emaciation,debility,andmuscletension.
https://www.mdpi.com/1420-3049/14/7/2373/htm

3. Aswagandha In Ayurveda
3
Italsohelpscounteractchronicfatigue,weakness,dehydration,boneweakness,looseteeth,thirst,
impotency,prematureageing,emaciation,debility,andmuscletension.
TheleavesoftheplantarebitterintasteandusedasanaAnthelminticstheinfusionisgiveninfever.
Bruisedleavesandfruitsarelocallyappliedtotumorsandtubercularglands,carbunclesandulcers.
Therootsareusedasanutrientandhealthrestorativeinpregnantwomenandoldpeople.
Thedecoctionoftherootboiledwithmilkandgheeisrecommendedforcuringsterilityinwomen.
Therootsarealsousedinconstipation,seniledebility,rheumatism,generaldebility,nervousexhaustion,
lossofmemory,lossofmuscularenergyandspermatorrhoea.
https://www.mdpi.com/1420-3049/14/7/2373/htm

4. 4
Theplantcontainsarangeofdifferentclassesofchemicalconstituentssuchasalkaloids,
steroidallactones,andflavonoids.
Allchemicalslistedpertaintotherootunlessotherwisespecified,astherootisthepartused.
Anaferine(Alkaloid),Anahygrine(Alkaloid),Beta-Sisterol,Chlorogenicacid(inleafonly),Cysteine(infruit),
Cuscohygrine(Alkaloid),Iron,Pseudotropine(Alkaloid),Scopoletin,Somniferinine(Alkaloid),Somniferiene
(Alkaloid),Tropanol(Alkaloid),Withanine(Alkaloid),Withananine(Alkaloid)andWithanolidesA-Y(Steroidal
lactones).
Themainconstituentsofashwagandhaarealkaloidsandsteroidallactones.Amongthevariousalkaloids,
withanineisthemainconstituent.Theotheralkaloidsaresomniferine,somnine,somniferinine,withananine,
pseudo-withanine,tropine,pseudo-tropine,3-a-gloyloxytropane,choline,cuscohygrine,isopelletierine,
anaferineandanahydrine.Twoacylsterylglucosideviz.SitoindosideVIIandsitoindosideVIIIhavebeen
isolatedfromroot.Theleavescontainsteroidallactones,whicharecommonlycalledwithanolides.The
withanolideshaveC28steroidalnucleuswithC9sidechain,havingsixmemberedlactonering.
Active Constituents

5. 5
Accumulation Of Three Important Bioactive Compounds In Different Plant Parts Of Withania Somnifera And Its
Determination By The LC-ESI-MS-MS (MRM) Method
Acomprehensiveexperimentwasconductedtostudytheaccumulationpatternanddeterminationofthree
importantbioactivecompoundsnamelywithaferin-A(WA),12-deoxywithastramonolide(WO)and
withanolide-A(WD)anditsdeterminationbytheliquidchromatography/electrosprayionizationtandemmass
spectrometry(LC-ESI-MS-MS)methodinroot,stem,fruitsandleavesofWithaniasomnifera.Arapidandsensitive
LC-ESI-MS-MSmethodwasdevelopedandvalidatedforthedeterminationofthesethreeimportantbioactive
compounds,havingsamemolecularweight.
Themultiplereactionmonitoringmethodwasestablishedbytwotransitionsforeachanalyteandintense
transitionusedforquantification.Separationofthethreeanalyteswasachievedwithinaruntimeof5minonan
RP-18columnusingamobilephaseconsistingofacetonitrileand0.1%aceticacidinwaterinanisocratic
condition.
ThedevelopedmethodwasvalidatedaspertheICHguidelines.Thedevelopedmethodwasfoundtobesuitablefor
identificationandquantificationofWA,WOandWDindifferentplantpartssuchasroots,stems,fruitsandleaves
ofW.somnifera.TheaccumulationofWAwashighestinleavessamples(8.84±0.37mg/g)anditwas2.23,5.85
and27.26timeshigherthanitsconcentrationinfruits,stemsandroots,respectively.WOandWDcontentswere
highest(0.44±0.016and0.72±0.016mg/g,respectively)inroot.

6. Chemical Constituents
6
ThechemistryofWithaniaspecieshasbeenextensivelystudiedandseveralgroupsofchemicalconstituentssuch
assteroidallactones,alkaloids,flavonoids,tanninetc.havebeenidentified,extracted,andisolated.Atpresent,
morethan12alkaloids,40withanolides,andseveralsitoindosides(awithanolidecontainingaglucosemolecule
atcarbon27)havebeenisolatedandreportedfromaerialparts,rootsandberriesofWithaniaspecies.Themajor
chemicalconstituentsoftheseplants,withanolides,aremainlylocalizedinleaves,andtheirconcentration
usuallyrangesfrom0.001to0.5%dryweight(DW).
ThewithanolidesareagroupofnaturallyoccurringC28-steroidallactonesbuiltonanintactorrearranged
ergostaneframework,inwhichC-22andC-26areappropriatelyoxidizedtoformasix-memberedlactonering.
Thebasicstructure)isdesignatedasthewithanolideskeleton.
WithaferinA(4β,27-dihydroxy-1-oxo-5β,6β-epoxywitha-2-24-dienolide,wasthefirstmemberofthisgroupof
compoundstobeisolated.WithaferinAistotallyabsentinroots,stems,seedsandpersistentcalyxoffruitsof
intactplantsbutpresentinleaves.Todayover130withanolidesfromSolanaceaegeneraareknown,mostly
occurringinfreeform,butinafewcasesalsoasglycosides.

7. Other Compounds
7
ExaminationofW.somniferarootshasresultedintheisolationofanewdimericthiowithanolide,named
ashwagandhanolide.Abioassay-guidedpurificationofthemethanolicextractofW.somniferafruitsyielded
withanamidesA-I.
IntheirquantitativeanalysisofIndianchemotypesofW.somniferabyTLCdensitometry,Guptaetal.detected
alkaloidsinalltheabovementionedplantparts,withthehighestcontentfoundinleaves.Thisisincontrasttothe
generalbeliefthattropanealkaloidsarerestrictedtotherootsofWithaniaspp.Extractionwith45%alcoholyields
thehighestpercentageofalkaloids.
Theisolationofnicotine,somniferine,somniferinine,withanine,withananine,pseudowithanine,tropine,
pseudotropine,3α-tigloyloxytropane,choline,cuscohygrine,dl-isopelletierineandnewalkaloidsanaferineand
anhygrinehasbeendescribed.ThereportedtotalalkaloidcontentintherootsofIndianW.somniferavaries
between0.13and0.31%,thoughmuchhigheryields(upto4.3%)havebeenrecordedinplantsofother
regions/countries.Inadditiontothealkaloids,therootsarereportedtocontainstarch,reducingsugars,
hentriacontane,glycosides,dulcitol,withanicil,anacidandaneutralcompound.Theleavesarereportedtocontain
fiveunidentifiedalkaloids(yield0.09%),chlorogenicacid,calystegines(nitrogen-containingpolyhydroxylated
heterocycliccompounds)withanone,condensedtanninandflavonoids.Theberrieshaveaminoacids.Fourtypesof
peroxidaseshavebeenpurifiedandcharacterizedfromW.somniferaroots.
https://www.mdpi.com/1420-3049/14/7/2373/htm

8. Market Sample-COA

9. 9
Plant Part Used: Root

10. 10
Plant Part: Whole plant

11. 11
Withanolides
About35withanolideshavebeenisolatedfromtherootsofW.somniferaofwhichwithanosideV(WSV),
withaferinA,withanolideA(WNA)andwithanolideB(WNB)arethemajorcomponents.WithaferinAhas
anti-tumor,apoptotic,anti-angiogenesis,radiosensitizingandanti-inflammatoryactivities.WNAis
effectiveasaneurological,immunologicalandanti-stressagent.WSIVandVplayanimportantneuro-
regenerativerole.ThusinspinalcordinjuryWSIVandVimprovehindlimbfunctionandincreasethe
myelinlayerintheperipheralnervoussystem.Inthelightofthis,itisimportanttofindoutthe
bioavailabilityoftheindividualwithanolidecompoundstoascertaintheirtherapeuticefficacy.
CONCLUSIONS
Basedonthepresentstudiesontheabsorptioncharacteristicsofthetestedwithanolidesitmaybe
concludedthatWNA,WNN,1,2DWMandWNBwerehighlypermeable;whereasWSIV,andWSV
showedlowpermeable.SurprisinglyWFA,thehighlybiologicallyactivewithanolidewasfoundtobe
eitherimpermeableormetabolizedonpassingthroughthecelllayer.ItislikelythatabsorptionofWFA
invivoisacomplexprocessandpossiblyasystememployingCaco-2cellscouldprovidebetterinsight
intheabsorptioncharacteristicsofWFA.

12. 12
Withanolides
Withanolideshavereceivedsignificantattentionduetotheirversatilebiologicalactivitiesdemonstratedinvitro
and/orinvivo.Theseactivitieshavebeendescribedasantitumor,cytotoxic,apoptotic,anti-inflammatory,
immunomodulating,antimicrobial,antistress,antioxidant,anti-neurodegenerative,radiosensitizing,and
insectantifeedant.WithaferinA,themoststudiedwithanolide,possessesawidearrayofthepharmacological
activitiesdescribedaboveandthuscarriesagreatclinicalpotentialfordrugdevelopment.
Mostnotably,theantitumorandassociatedanti-inflammatoryactivitiesofWAandotherwithanolidesresults
fromtargetingmultiplesignalingpathwayssimultaneously,particularlythenuclearfactorkappaB(NF-κB),
signaltransducerandactivatoroftranscription(STAT),andubiquitinproteasomepathways.Thepotent
biologicalactivitiesofwithanolidessuchasWAandtubocapsenolideA,especiallytheantitumorandanti-
inflammatorypropertieshavebeenattributedtothepresenceofkeystructuralfeaturessuchasanα,β-
unsaturatedketoneinringA,a5β,6β-epoxideinringB,andalactonesidechain[1,4,7,13,30,58–62].
Cysteineresiduesintheproteinsareoftenimplicatedtoreactwiththesekeyelectrophilicsitesonthe
withanolidemolecule.Whileotherwithanolidesmaypossessα,β-unsaturatedketoneand/orepoxideinsome
respect(e.g.,paraminabeolides,capsisteroids,andchantriolides)andarebioactive,theyaregenerallyless
potentthanthosewithanolidespossessingallthreecrucialfunctionalgroups.

13. 13
InadditiontotheinhibitionofNF-κBactivation,WAandseveralotherwithanolideshavebeenshownto
directlyblocktheexpressionofLPS-orTNFα-inducedNF-κB-regulatedinflammatorygenessuchasiNOS,
COX-1,COX-2,andNO.NitricoxideisasmallmoleculethatregulatesMMPs(matrixmetalloproteinases)and
jointsextracellularmatrix,andismodulatedthroughiNOS.COX-1andCOX-2convertarachidonicacidto
prostaglandins,whichinturncauseasignificantinflammatoryresponse.COX-1isconstitutivelyexpressedin
mostcelltypes,andisresponsibleformaintenanceofnormalphysiologicfunction,whereasCOX-2is
inducibleinresponsetoproinflammatorycytokines.
WithaferinA,viscosalactoneB,2,3-dihydrowithaferinA,and4-(2,2-dimethyl-3-oxocyclopropoxy)-2,3-
dihydrowithaferinAwereshowntoinhibitCOX-2enzymebutnotCOX-1.Likeotherwithanolides,withanolide
sulfoxide,asulfoxidedimerofWAwashighlyselectiveininhibitingCOX-2comparedtoCOX-1.
Withanolides

14. Modulation Of The AP-1 Pathway By Withanolides
14
ThetranscriptionfactorAP-1,whichplaysakeyroleintheinflammatoryresponseisimplicatedinseveral
diseasessuchascancer,psoriasis,inflammatoryboweldisease(IBD),rheumatoidarthritis(RA)and
fibrosis.TheAP-1complexconsistsofhomoandheterodimersofJun(JunD,C-Jun,andJunB)andtheFos
(FosB,C-Fos,Fra-1andFra-2)familyofproteins.Cytokines,chemokines,hormones,andgrowthfactorsas
wellasexternalstressfactorsareknowntoactivateAP-1signaling.TheAP-1complextranslocatestothe
nucleusinresponsetostresssignalingcascades,suchMAPKsandc-Junterminalkinases.
ThisinturnleadstoactivationofAP-1andregulatesmultiplefunctionssuchasdifferentiation,
transformation,proliferation,andsurvival.ThecrudeethanolextractofWShasbeenshowntoinhibitthe
nuclearlocalizationofbothAP-1andNF-κBinLPS-activatedperipheralbloodmononuclearcells(PBMC)
ofbothnormalandRApatients,aswellassynovialfluidmononuclearcells(SFMC)ofRApatients.Thisin
turnledtodecreaseddownstreamtranscriptiontargetgenessuchasMMPs,COX-2,andiNOS,allofwhich
areknownmediatorsofRA.

15. Withanolides Can Modulate The PPARγ Pathway
15
PPARγplaysakeyroleininflammationthroughmodulationofproinflammatorytranscriptionfactorssuch
asNF-κBandAP-1.Treatmentof3T3-L1adipocyteswithWAresultedinphosphorylationofextracellular
signal-regulatedkinase(ERK),followedbydecreasedexpressionsofPPARγleadingtoalteredlevelsofBcl2
andBaxexpression,inductionofapoptosis,andinhibitionofadipogenesis.

16. Modulation Of The Hsp90 Pathway By Withanolides
16
Heatshockproteins(Hsp)areATP-dependentubiquitouslyexpressedmolecularchaperonesthatare
involvedinthefolding,assembly,maintenance,andtransportofkeyregulatoryproteinsinvolvedin
numeroussignalingpathwaysinthecell.Severalenvironmentalandphysiologicalstimulisuchas
hypoxia,oxidativedamage,inflammation,infection,andelevatedtemperatureinducethe
expressionofthesehighlyconservedmolecularchaperonefamilyofproteinsasaprotein
homeostasisandsurvivalresponse.TheHsp90familyofproteins(Hsp90α,Hsp90β,GRP94,
andTRAP1)formalargecomplexwithotherco-chaperonessuchascdc37,HSP70-HSP90
organizingprotein,p27,Hsp32,andHsp70.Thiscomplexthenstabilizesandmaintainsfunctional
activityofproteins/kinasesinmanykeysignalingpathways,suchasPI3K/Akt/mTOR,p38/MAPK,and
NF-κB,allofwhichplaycriticalrolesininflammation,chronicinflammatorydiseases,andoncogenesis.
ThroughinhibitionofHsp90,andthereforeinhibitionofitsoncogenicchaperoneclients,cancercells
undergoapoptosis.
SeveralstudieshaveshownthatwithanolidessuchasWA,withalongolidesAandB,tubocapsenolideA,
andsomeoftheirsyntheticallymodifiedanalogessuchaswithalongolideAtriacetateand
withalongolideBdiacetateareareabletotargetmultiplecancerssuchascolon,prostate,brain,breast,
headandneck,skin,adrenal,andthyroidbothinvitroandinvivo.WithanolidessuchasWAand
withalongolideAareknowntoblockHsp90chaperonefunctionthroughblockingtheHsp90/cdc37
complex,andinductionofthiol-mediatedoxidativestress.

17. Withanolide Modulation Of Nrf 2 Pathway
17
Nuclearfactorerythroid2relatedfactor2(Nrf2)isatranscriptionfactorthatregulatesgenesinvolvedin
redoxhomeostasis,inflammation,energymetabolismandcellulargrowth.Nrf2isengagedincrosstalkwith
severalsignalingpathwaysthatplayacriticalroleinthepathogenesisandprogressionofchronicdiseases,
includingNF-κB,PI3K,MAPK,glycogensynthasekinase-3β,andnotch.
MoleculardockingstudieshaveshownthatbothWAandwithanoneinteractwiththeaminoacidsAla69,
Gln75,andPhe71ofNrf2.Inanotherstudy,WAinducedreactiveoxygenspecies(ROS)that
activatedJNKandstabilizedNrf2thatresultedinactivationofNADPHquinoneoxidoreductase
andTap73transcriptionalfunctionleadingtoapoptosisofcancercells.WAwasalsoshownto
inhibitNFκB,AP-1,andNrf2inadriamycin-resistanthumanmyelogenouserythroleukemic
K562/Adrcellsinadose-dependentmanner.

18. Modulation Of The HIF-1 Pathway By Withanolides
18
TranscriptionalactivationofHIF-1upregulatesseveralgenesthatcontrolglycolyticmetabolism,
angiogenesis,invasion,metastasis,andcellsurvival,suchasVEGF,MMPs,stromalcell-derivedfactor-1,e-
cadherin,chemokinereceptor4,EGF,andtransforminggrowthfactorbeta(TGF-β)3.Crosstalkbetween
NF-κBandHIFpathwayshasbeenshowntobeassociatedwithseveralchronicinflammatorydiseases
suchascancer,RA,asthma,andchronicobstructivepulmonarydiseases.
Insolidtumors,theavailabilityofoxygenwithinthetumordecreasesasdistancefrombloodvessels
increasesresultinginthecreationofhypoxicregions.Thisisknowntoberesponsibleinpartfortherapy
resistanceandmetastaticspread.Although,nostudythusfardirectlydemonstratesinhibitionofHIF-1
transcriptionalactivationbywithanolides,afewnotedownregulationofmigration-promotingHIF-
mediatedgenessuchasVEGF,heterogeneousnuclearribonucleoproteinK(hnRNP-K)andMMPs,which
leadtorestrictionofangiogenesisandmetastasis.

19. Summary
19
Studiesshowtheabilityofwithanolidestotargetmultipleinterconnectedsignalingpathwayssuchas
PI3K/Akt/mTOR,JAK/STAT,AP-1,NF-κB,PPARγ,Nrf2andMAPK.Withanolidestargetthesepathways
throughmultiplemechanism,suchasblockingHsp90-Cdc37co-chaperoneinteraction,targetingAkt
anditsdownstreampathways,andinductionofthiol-mediatedoxidativestress.
Eachofthesemechanismsandpathwayinteractionsplayimportantrolesinthedevelopmentof
chronicinflammatorydiseases.Buildingonthestudiesidentifyingmechanismsofactionof
withanolides,wewilldiscusstheclinicalimportanceofwithanolidesoninflammatorymediated
diseasesincludingchronicinflammatory/autoimmune,cancer,andneurologic.

20. 20
Schematic Diagram Representing Modulation Of Various Inflammatory Pathways By Withanolides
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121644/

21. Anti-Stress
21
ThisresearchconfirmsthetheorythatAshwagandhahasasignificantanti-stressadaptogeniceffect.
ResearchconductedattheDepartmentofPharmacology,UniversityofTexasHealthScienceCenterindicated
thatextractsofAshwagandhaproduceGABA-likeactivity,whichmayaccountfortheherb'santi-anxiety
effects.
GABA(GammaAmino-butyricacid)isaninhibitoryneurotransmitterinthebrain.Itsfunctionistodecrease
neuronactivityandinhibitnervecellsfromoverfiring.Thisactionproducesacalmingeffect.Excessive
neuronalactivitycanleadtorestlessnessandinsomnia,butGABAinhibitsthenumberofnervecellsthatfire
inthebrain,andhelpstoinducesleep,upliftmood,andreduceanxiety.
Ashwagandhahastraditionallybeenusedtostabilizemoodinpatientswithbehavioraldisturbances.
Researchhasrevealedthattheherbproducesananti-depressantandanti-anxietyeffectinrodents
comparabletotheanti-depressantdrugimipramineandtheanti-anxietydruglorazepam(Ativan).

22. Anti-Stress
22
Infact,AshwagandhaisoneofthemostwidespreadtranquillizersusedinIndia,whereitholdsapositionof
importancesimilartoginsenginChina.Itactsmainlyonthereproductiveandnervoussystems,havinga
rejuvenativeeffectonthebody,andisusedtoimprovevitalityandaidrecoveryafterchronicillness.
ResearchresultsshowedthatbothAshwagandhaandPanaxginsengdecreasedthefrequencyandseverityof
stress-inducedulcers,reversedstress-inducedinhibitionofmalesexualbehavior,andinhibitedtheeffectsof
chronicstressonretentionoflearnedtasks.Bothbotanicalsalsoreversedstress-induced
immunosuppression,butonlytheWithaniaextractincreasedperitonealmacrophageactivity.
Withaniasomnifera,however,hasanadvantageoverPanaxginsenginthatitdoesnotappeartoresultin
.ginseng-abusesyndrome.,aconditioncharacterizedbyhighbloodpressure,waterretention,muscletension,
andinsomnia.

23. Antibiotic Activity
23
https://www.rroij.com/open-access/a-review-on-pharmacological-profile-of-
withania-somnifera-ashwagandha.php?aid=33844
Theantibioticactivityoftherootsaswellasleaveshasrecentlybeenshownexperimentally.WithaferinAin
concentrationof10μg/mlinhibitedthegrowthofvariousGram-positivebacteria,acid-fastandaerobic
bacilli,andpathogenicfungi.ItwasactiveagainstMicrococcuspyogenesvaraureusandpartiallyinhibited
theactivityofBacillussubtilisglucose-6-phosphatedehydrogenase.
WithaferinAinhibitedRanikhetvirus.AntibioticactivityofWithaferinAisduetothepresenceofthe
unsaturatedlactone-ring.Thelactoneshowedstrongtherapeuticactivityinexperimentallyinduced
abscessesinrabbits,thebeingsomewhatstrongerthanthatofPenicillin.Itsubstantiatesthereputationof
theleavesasacureforulcersandcarbunclesintheindigenoussystemofmedicine.

24. Antioxidant Effect
24
https://www.rroij.com/open-access/a-review-on-pharmacological-profile-of-
withania-somnifera-ashwagandha.php?aid=33844
Freeradicaldamageofnervoustissuemaybeinvolvedinnormalagingandneurodegenerative
diseases,e.g.,epilepsy,schizophrenia,Parkinson’s,Alzheimer’s,andotherdiseases.
TheactiveprinciplesofWS,sitoindosidesVII-XandwithaferinA(glycowithanolides),havebeen
testedforantioxidantactivityusingthemajorfree-radicalscavengingenzymes,superoxide
dismutase(SOD),catalase(CAT),andglutathioneperoxidase(GPX)levelsintheratbrainfrontal
cortexandstriatum.
Decreasedactivityoftheseenzymesleadstoaccumulationoftoxicoxidativefreeradicalsand
resultingdegenerativeeffects.Anincreaseintheseenzymeswouldrepresentincreased
antioxidantactivityandaprotectiveeffectonneuronaltissue.

25. Anti-aging Activity
25
Ashwagandhawastestedforitsanti-agingpropertiesinadouble-blindclinicaltrial.
https://www.rroij.com/open-access/a-review-on-pharmacological-profile-of-withania-
somnifera-ashwagandha.php?aid=33844

26. Nootropic Effect
26
ChronicWSadministrationsignificantlyreversedreserpine-inducedretentiondeficits.Indifferentstudy
withWSrootextractimprovedretentionofapassiveavoidancetaskinastep-downparadigminmice.WS
alsoreversedthescopolamine-induceddisruptionofacquisitionandretentionandattenuatedtheamnesia
producedbyacutetreatmentwithelectroconvulsiveshock(ECS),immediatelyaftertraining.
ChronictreatmentwithECS,for6successivedaysat24hintervals,disruptedmemoryconsolidationonday
7.DailyadministrationofWSfor6dayssignificantlyimprovedmemoryconsolidationinmicereceiving
chronicECStreatment.WS,administeredonday7,alsoattenuatedthedisruptionofmemoryconsolidation
producedbychronictreatmentwithECS.Ontheelevatedplus-maze,WSreversedthescopolamine-induced
delayintransferlatencyonday1.Onthebasisofthesefindings,itissuggestedthatWSexhibitsa
nootropic-likeeffectinnaïveandamnesicmice.

27. Nootropic Effect
27
EffectsofsitoindosidesVII-Xandwithaferinisolatedfromaqueousmethanolextractofrootsofcultivated
varietiesofWSwerestudiedonbraincholinergic,glutamatergicandGABAergicreceptorsinrats.The
compoundsslightlyenhancedacetylcholinesterase(AChE)activityinthelateralseptumandglobuspallidus,
anddecreasedAChEactivityintheverticaldiagonalband.
OraladministrationofwithanosideIVsignificantlyimprovedmemorydeficitsinAbeta-injectedmiceand
preventedlossofaxons,dendrites,andsynapses.Sominone,anaglyconeofwithanosideIV,wasidentifiedas
themainmetaboliteafteroraladministrationofwithanosideIV.
WithanosideIVmayameliorateneuronaldysfunctioninAlzheimer'sdiseaseandthattheactiveprincipleafter
metabolismissominone.Inanotherstudyreserpinetreatedanimalsalsoshowedpoorretentionofmemoryin
theelevatedplusmazetaskparadigm.

28. Antiparkinsonian Properties
28
https://www.rroij.com/open-access/a-review-on-pharmacological-profile-of-withania-
somnifera-ashwagandha.php?aid=33844
AntiparkinsonianeffectsofWSextracthasbeenreportedduetopotentantioxidant,
antiperoxidativeandfreeradicalquenchingpropertiesinvariousdiseasedconditions.ofWSG,
ratherthanitsGABA-mimeticactionreportedforthepreventionofhaloperidol-inducedTD.
WSsignificantlyreversedthecatalepsy,tardivedyskinesiaand6-Hydroxydopamineelicitedtoxic
manifestationsandmayofferanewtherapeuticapproachtothetreatmentofParkinson'sdisease.

29. Withanolides
29
About35withanolideshavebeenisolatedfromtherootsofW.somniferaofwhichwithanosideV(WS
V),withaferinA,withanolideA(WNA)andwithanolideB(WNB)arethemajorcomponents.
WithaferinAhasanti-tumor,apoptotic,anti-angiogenesis,radiosensitizingandanti-inflammatory
activities.
WNAiseffectiveasaneurological,immunologicalandanti-stressagent.WSIVandVplayanimportant
neuro-regenerativerole.ThusinspinalcordinjuryWSIVandVimprovehindlimbfunctionandincrease
themyelinlayerintheperipheralnervoussystem.Inthelightofthis,itisimportanttofindoutthe
bioavailabilityoftheindividualwithanolidecompoundstoascertaintheirtherapeuticefficacy.

30. Bioavailability
30
Basedonthepresentstudiesontheabsorptioncharacteristicsofthetestedwithanolidesitmaybe
concludedthatWNA,WNN,1,2DWMandWNBwerehighlypermeable;whereasWSIV,andWSVshowed
lowpermeable.SurprisinglyWFA,thehighlybiologicallyactivewithanolidewasfoundtobeeither
impermeableormetabolizedonpassingthroughthecelllayer.ItislikelythatabsorptionofWFAinvivoisa
complexprocessandpossiblyasystememployingCaco-2cellscouldprovidebetterinsightintheabsorption
characteristicsofWFA.

31. 31
Conclusions
Basedonthepresentstudiesontheabsorptioncharacteristicsofthetestedwithanolidesitmaybe
concludedthatWNA,WNN,1,2DWMandWNBwerehighlypermeable;whereasWSIV,andWSVshowed
lowpermeable.SurprisinglyWFA,thehighlybiologicallyactivewithanolidewasfoundtobeeither
impermeableormetabolizedonpassingthroughthecelllayer.ItislikelythatabsorptionofWFAinvivoisa
complexprocessandpossiblyasystememployingCaco-2cellscouldprovidebetterinsightintheabsorption
characteristicsofWFA.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630722/

32. Withanolide A
32
Withanolide A is sparingly soluble in aqueous solutions. To enhance aqueous solubility , dilute the organic
solvent solution into aqueous buffers or isotonic saline .
If performing biological experiments, ensure the residual amount of organic solvent is insignificant , since
organic solvents may have physiology effects at low concentrations. We do not recommend storing the
aqueous solution for more than one day.

33. Thank You
Business Development Team
[phone]
[email protected]
www.stabicon.com