Cyclooxygenase-2 enzyme inhibitory withanolides from Withania somnifera leaves

Four novel withanolide glycosides and a withanolide have been isolated from the leaves of Withania somnifera. The structures of the novel compounds were elucidated as physagulin D (1→6)-β-d-glucopyranosyl-(1→4)-β-d-glucopyranoside (), 27-O-β-d-glucopyranosyl physagulin D (), 27-O-β-d-glucopyranosyl viscosalactone B (), 4,16-dihydroxy-5β, 6β-epoxyphysagulin D (), and 4-(1-hydroxy-2,2-dimethylcyclo-propanone)-2,3-dihydrowithaferin A () on the basis of 1D-, 2D NMR and MS spectral data. In addition, seven known withanolides withaferin A (), 2,3-dihydrowithaferin A (), viscosalactone B (), 27-desoxy-24,25-dihydrowithaferin A (), sitoindoside IX (), physagulin D (), and withanoside IV () were isolated. These withanolides were assayed to determine their ability to inhibit cycloxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes and lipid peroxidation. The withanolides tested, except compound , showed selective COX-2 enzyme inhibition ranging from 9 to 40% at 100 μg/ml. Compounds , and also inhibited lipid peroxidation by 40, 44 and 55%, respectively. The inhibition of COX-2 enzyme by withanolides is reported here for the first time.