Ashwagandhanolide, a Bioactive Dimeric Thiowithanolide Isolated from the Roots of Withania somnifera

Abstract

A new dimeric withanolide, ashwagandhanolide (1), was isolated from the roots of an Ayurvedic medicinal herb, Withania somnifera. A detailed spectroscopic evaluation revealed its identity as a dimer with an unusual thioether linkage. Compound 1 displayed growth inhibition against human gastric (AGS), breast (MCF-7), central nervous system (SF-268), colon (HCT-116), and lung (NCI H460) cancer cell lines, with IC50 values in the range 0.43-1.48 microg/mL. In addition, it inhibited lipid peroxidation and the activity of the enzyme cyclooxygenase-2 in vitro.

In vitro protective effects of Withania somnifera (L.) dunal root extract against hydrogen peroxide and β‐amyloid(1–42)‐induced cytotoxicity in differentiated PC12 cells

“…Indeed, component 32, detected in the W. somnifera extract by LC-MS n analysis ( Table 1, Fig. 5), showed mass spectral data consistent with the dimeric thiowithanolide, ashwagandhanolide, a compound reported to inhibit cell proliferation in various tumor cell lines (Subbaraju et al, 2006).…”

“…There is also evidence of neuroprotection by withanolide A, withanoside IV, and withanoside VI, steroidal derivatives isolated from a root extract of One in vitro study showed an interesting finding in which W. somnifera root extract significantly and dose-dependently increased the percentage of cells with neurites in human neuroblastoma SK-N-SH cells (Tohda et al, 2000). However, one observation in our study was that at high concentrations (> 100 µg/mL), the aqueous extract exhibited cytotoxic and perhaps anti-proliferative properties against the dPC12 cell line, (Subbaraju et al, 2006;Stan et al, 2008). Indeed, component 32, detected in the W. somnifera extract by LC-MS n analysis ( Table 1, Fig.…”

“…Inhibition of lipid peroxidation due to an antioxidant action has been observed both in vitro and in vivo with extracts of W. somnifera root and some of the component withanolides, including withaferin A (Dhuley, 1998;Panda et al, 1997;Bhattacharya et al, 2000;Chaurasia et al, 2000), a compound detected in the W. somnifera extract investigated in the present study. In addition to the withanolides having antioxidant capacity and decreasing lipid peroxidation in rodent brains, withanolides also enhanced catalase and glutathione peroxidase activities in rat frontal cortex and striatum (Chaurasia et al, 2000;Mishra et al, 2000;Scartezzini and Speroni, 2000;Bhattacharya et al, 1997 and2001;Subbaraju et al, 2006). In another 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 F o r P e e r R e v i e w 14 study, an extract of W. somnifera was associated with attenuation of memory loss induced by oxidative stress mediated by free radicals in an animal model (Parihar et al, 2004).…”

Withanolides and Related Steroids

“…Withaferin A (1), its diacetate, viscosalactone B (505), compound 6, and ashwagandhanolide (78) were the most active (IC 50 range 0.5-1 mM) and comparable in potency to a reference compound, adriamycin (47,240). Compound 78 also inhibited lipid peroxidation and the activity of the enzyme cyclooxygenase-2 in vitro.…”

Antiproliferation potential of withaferin A on human osteosarcoma cells via the inhibition of G2/M checkpoint proteins

“…Among the reported withanolides, withaferin A (WA) (16) (as seen in Fig. 1) and ashwagandhanolide (17), obtained from the leaves and roots, respectively, are well-known potent secondary metabolites of W. somnifera and are reported to possess anticancer properties. Antiproliferative, antimetastatic, antiangiogenic, anti-invasive and proapoptotic activities of withanolides have been reported, with the underlying mechanism found to be associated with the suppression of nuclear factor (NF)-κB and NF-κB-regulated gene products (18).…”