## Introduction
### Chemical constituents
#### Pharmacological activities of withanolides
somnifera_ caused suppression of a2-macroglobulin, an indicator for antiinflammatory drugs in rat serum inflamed by injection of carrageenanen suspension [64]. The extracts also caused a significant reduction in both paw swelling and bony degenerative changes in [PERSON]'s adjuvant-induced arthritis as observed by radiological examination [65]. Rats injected with formalize in the hind leg footpad showed decreased absorption of \({}^{14}\)C-glucose in rat jejunum, glucose absorption being maintained at the normal level by _Withania_ extracts, which produced an antiinflammatory effect [66]. The traditional antihyperglycemic and antidyslipidemic activities of _W. coagulans_, popularly known as Indian cheese marker, have been recently confirmed [67]. Withanolides isolated from _W. coagulans_ fruits show significant inhibition of the postprandial rise in hyperglycemia post-sucrose load in normoglycemic rats as well as streptozotocin-induced diabetic rats. _W. somnifera_ extracts have a chemopre effect on skin cancer in mice induced by 7,12-dimethylbenz[a]antracene. This activity is thought to be partly due to the antioxidant/free radical scavenging activity of the extract [68]. Recently, bioactive properties of withaferin A have been reported: cytoskeletal architecture alteration by covalently binding annexin II [69], antitumor capacity by inhibition of proteasomal chymotrypsin-like activity [70], and apoptosis induction through the inhibition of protein kinase C [71]. In relation to the apoptosis-inducing mechanism of withaferin A, [PERSON] _et al_. [72] have demonstrated that it is associated with the activation of caspase-3 and the translocation of cytochrome \(c\) from the mitochondria to the cytosol, as well as the cleavage of PLC-\(\gamma\)1 (a substrate protein of caspases), whereas ectopic expression of Bcl-2 oncoprotein significantly attenuates withaferin A-induced apoptosis. _Withania_ alkaloids have a prolonged hypotensive, bradycardia and respiratory-stimulant action in dogs [73]. It has been found that the hypotensive effect is mainly due to autonomic ganglion blocking action as well as a depressant action on the higher cerebral centers. The alkaloid stimulates the vasomotor and respiratory centers in the brain stem of the dogs. The cardio-inhibitory action appeared to be due to ganglion blocking and direct cardio-depressant actions. **A biotechnological approach to withanolide production**  
Many biotechnological studies of _Withania_ species, especially _W. somifera_, have been carried out to enhance the production of their active compounds. Large-scale plant cell cultures may be cost-effective and also allow the production of higher amounts of withanolides in a relatively short period of time. Tissue cultures of an Indian chemotype of _W. somifera_ from axillary meristems using MS agar medium supplemented with 2,4-D, IAA, NAA, BA, coconut milk or kinetin, either alone or in combination, have been reported [74]. Calli were formed on medium containing 2.0 mg 2,4-D/L and 0.2 mg Kin/L. Suspension cultures were initiated from callus tissue in liquid MS medium supplemented with 2.0 mg 2,4-D/L, 0.2 mg Kin/L and 2.0 mg BA/L. Multiple shoot cultures were also grown in MS agar medium containing 2.0 mg BA/L. Callus cultures failed to synthesize withanolides, but multiple shoot cultures synthesized significant amounts; their concentrations were highest with 2.0 mg BA/L and 10% coconut milk. Multiple shoot cultures of _W. somifera_ from single shoot tip explants and their potential for the production of withaferin A and withanolide D have also been investigated [75]. Shoot tips grown on MS medium supplemented with BA (1 mg/l) induced 10.0 microshoots per explant and shoot cultures accumulated withaferin A (0.04 %) and withanolide D (0.06%). Supplementation of MS solid agar medium with 1.0 mg BA/L and 4% sucrose enhanced accumulation of both withaferin A (0.16%) and withanolide D (0.08 %).