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 μm with no activity against COX-1 enzyme. The IC₅₀ values of compound 1 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 γm. Both S-containing dimeric withanolides, 1 and 2, completely suppressed TNF-induced NF-κB activation when tested at 100 μm. 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-κB activation for compounds 1 and 2.