Withaferin from Withania somnifera

The withanolides are steroidal lactones built on an ergostane skeleton of 28 carbons functionalized at carbons 1, 22 and 26, commonly known as the withanolide skeleton. The first withanolide to be isolated and characterized was withaferin A, Fig. (1), isolated in 1965 almost simultaneously by Lavie from Withania somnifera and by Kupchan from... 

Kuroyanagi and his coworkers evaluated a series of sixteen withanolides, isolated from Withania somnifera, for their cell differentiation inducing ability and found that withaferin A (2), withanolide D (24), dihydrowithanolide D (59), and 27-hydroxywithanolide D (60) were potent cell differentiation inducers against the Ml cells [83]. It was further concluded that all these withanolides have a similar 4)S-hydroxy-5) -6)S-epoxy-2-ene-l-one moiety in ring A, apparently responsible for their cell differentiation inducing activity. 

However, withaferin-A, which was the first active principle isolated from Withania somnifera and also constituted the first member of a new class of phytosteroids (the withanolides), produced immunosuppression. Thus, it inhibited adjuvant arthritis in rats, graft vs host reaction in chicken, xenograft vs host reaction in mice, and depleted murine splenic cells in vitro [38-41]. This effect has been attributed to the glucocorticoid-like structure of withaferin-A [39]. Withania somnifera also reduces acute phase reactants [8] as well as a2-macroglobulin during inflammation. 

Yang DTC, Wilson BJ, Harris TM (1971) The structure of ipomeamaranol A new toxic furan-osesquiterpene from moldy sweet potatoes. Phytochemistry 10 1653-1654 Yarden A, Lavie D (1962) Constituents of Withania somnifera. I. Functioned groups of withaferin. J Chem Soc 2925-2927... 

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