RESUMEN
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.
Asunto(s)
Proliferación Celular/efectos de los fármacos , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 2/metabolismo , FN-kappa B/antagonistas & inhibidores , Sulfóxidos/farmacología , Witanólidos/farmacología , Línea Celular Tumoral , Ergosterol/análogos & derivados , Ergosterol/farmacología , Humanos , Estructura Molecular , Extractos Vegetales/farmacología , Raíces de Plantas/química , Sulfóxidos/aislamiento & purificación , Withania/química , Witanólidos/aislamiento & purificaciónRESUMEN
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.
Asunto(s)
Bacopa/química , Cromatografía Líquida de Alta Presión/métodos , Glicósidos/química , Animales , Artemia/efectos de los fármacos , Secuencia de Carbohidratos , Técnicas de Química Analítica/métodos , Glicósidos/aislamiento & purificación , Glicósidos/farmacología , Espectroscopía de Resonancia Magnética , Datos de Secuencia Molecular , Estructura Molecular , Saponinas/química , Saponinas/aislamiento & purificación , Saponinas/farmacología , Espectrofotometría Infrarroja , Triterpenos/química , Triterpenos/aislamiento & purificación , Triterpenos/farmacologíaRESUMEN
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.