## Introduction
### Chemical constituents
#### Pharmacological activities of withanolides  
The pharmacological activity of _W. somnifera_ extracts has been summarized recently by [PERSON] and [PERSON] [49]. Historically, _W. somnifera_ has been used as an antioxidant, adaptogen, aphrodisiac, liver tonic, antiinflammatory agent and astringent and more recently as an antibacterial, antihyperplycemic and antitumoral, as well as to treat ulcers and senile dementia. The active principles of _W. somnifera_ have been tested for antioxidant activity by observing the levels of the major free-radical scavenging enzymes, superoxide dismutase, catalase and glutathione peroxidase, in the rat brain frontal cortex and striatum. The increase in these enzymes after treatment with with ethanolides represent enhanced antioxidant activity and a corresponding protective effect on neuronal tissue, suggesting that the antioxidant effect of _W. somnifera_ in the brain may be responsible for its diverse pharmacological properties [51]. Similarly, oral administration of _W. somnifera_ extracts prevented an increase in lipid peroxidation in mice and rabbits [52]. Anxiolitic and antidepressant actions of the bioactive withanolides have been assessed in rats [53]. Withanolides reduced rat brain levels of tribulin (an endocoid marker of anxiety) when the levels of this compound were increased by administration of pentylenetetrazole, an anxiogenic agent. The antidepressant effect of withanolides is comparable with that induced by imipramine in the forced swim-induced \"behavioural despair\" and \"learned helpessness\" test. In a rat model withanolides were able to decrease the number and severity of chronic stress-induced ulcers, reverse chronic stress-induced inhibition of male sexual behavior, chronic stress-induced immunosuppression and also increased peritoneal macrophage activity [54]. It has also been demonstrated that methanolic extracts of _Withania_ reduce ulcer index, volume of gastric secretion, free acidity, and total acidity [55]. The effects of sitoindosides VII-X and withaferin isolated from aqueous methanol extracts of _W. somnifera_ roots were studied on brain cholinergic, glutamatergic and GABAergic receptors in rats. The data suggest the bioactive compounds preferentially influence events in the cortical and basal forebrain cholinergic-signal transduction cascade. The cognition-enhancing and memory-improving effects of _W. somnifera_ extracts can be partly explained by the drug-induced enhancement of cortical muscarinic acetylcholine receptor capacity [56]. In general, Ashawagandha has been used traditionally and commonly as a tonic and nootropic agent. It has also been associated with improvements in  
Figure 6: Cont. scopolamine-induced memory deficits in mice [57]. Methanolic extracts of the plant have been reported to induce neurite extension [58] and to contain withanolide A, withanoside IV and withanoside VI, which induce neurite outgrowth in human neuroblastoma SH-SY5Y [59]. In A(25-35)-induced damaged cortical neurons, withanolide A, withanoside IV and withanoside VI showed neuritic regeneration and synaptic reconstruction. Dentritic atrophy was completely prevented by treatment with these withanolides, particularly withanoside IV and VI [60]. Neuroleptic-induced catalelpsy has been used as an animal model for screening drugs for [PERSON] disease. Hope of treatment for this disease has been offered by the inhibitory effects of _W. somnifera_ extracts on haloperidol or reserpine-induced catalelpsy in mice [61]. The antiparkinsonian effect of _W. somnifera_ extracts has also been attributed to potent antioxidant, antiperoxidative and free radical quenching properties [62]. The extracts of _W. somnifera_ have shown antiinflammatory effects in a variety of rheumatological conditions, reducing, for example, [PERSON]'s complete adjuvant-induced inflammation in rats and decreasing to undetectable levels the \(\alpha\)2-glycoprotein found only in inflamed rat serum [63]. In another study, _W.