ABSTRACT
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 microm with no activity against COX-1 enzyme. The IC(50) 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 microm. Both S-containing dimeric withanolides, 1 and 2, completely suppressed TNF-induced NF-kappaB activation when tested at 100 microm. 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-kappaB activation for compounds 1 and 2.
Subject(s)
Cell Proliferation/drug effects , Cyclooxygenase 1/metabolism , Cyclooxygenase 2/metabolism , NF-kappa B/antagonists & inhibitors , Sulfoxides/pharmacology , Withanolides/pharmacology , Cell Line, Tumor , Ergosterol/analogs & derivatives , Ergosterol/pharmacology , Humans , Molecular Structure , Plant Extracts/pharmacology , Plant Roots/chemistry , Sulfoxides/isolation & purification , Withania/chemistry , Withanolides/isolation & purificationABSTRACT
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.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Cyclooxygenase Inhibitors/isolation & purification , Ergosterol/analogs & derivatives , Plants, Medicinal/chemistry , Withania/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Cyclooxygenase Inhibitors/chemistry , Cyclooxygenase Inhibitors/pharmacology , Drug Screening Assays, Antitumor , Ergosterol/chemistry , Ergosterol/isolation & purification , Ergosterol/pharmacology , Humans , India , Lipid Peroxidation/drug effects , Molecular Structure , Plant Roots/chemistryABSTRACT
Two triterpenoid glycosides have been isolated along with 10 known saponins from Bacopa monnieri. Structures of the compounds have been elucidated as 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] jujubogenin (1) and 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] pseudojujubogenin (2) by high resolution NMR spectral data and chemical correlations. Further, the chemical compositions of bacosides A and B have been delineated.
