Withanolide Sulfoxide from Aswagandha Roots Inhibits Nuclear Transcription Factor-Kappa-B, Cyclooxygenase and Tumor Cell Proliferation

Investigation of the methanol extract of Aswagandha (Withania somnifera) roots for bioactive constituents yielded a novel withanolide sulfoxide compound (1) along with a known withanolide dimer ashwagandhanolide (2) with an S-linkage. The structure of compound 1 was established by extensive NMR and MS experiments. Compound 1. was highly selective in inhibiting cyclooxygenase-2 (COX-2) enzyme by 60% at 100 mu m with no activity against COX-1 enzyme. The IC50 values of compound I against human gastric (AGS), breast (MCF-7), central nervous system (SF-268) and colon (HCT-116) cancer cell lines were in the range 0.74-3.63 mu m. Both S-containing dimeric withanolides, 1. and 2, completely suppressed TNF-induced NF-kappa B activation when tested at 100 mu m. The isolation of a withanolide sulfoxide from W. somnifera roots and its ability to inhibit COX-2 enzyme and to suppress human tumor cell proliferation are reported here for the first time. In addition, this is the first report on the abrogation of TNF-induced NF-kappa B activation for compounds I and 2. Copyright (C) 2009 John Wiley & Sons, Ltd.