New withanolides with anti-inflammatory activity from the leaves of Datura metel L.

Twenty three undescribed withanolides, daturmetelides A-W (1-23), were isolated from 70% EtOH extract of the leaves of Datura metel L. The structural characterizations and relative configurations of 1-23 were elucidated by extensive spectroscopic analysis as well as by comparison with literature values. The absolute configurations of 1 and 3 were determined by X-ray crystallography. Bioassay results showed that 1 and 7 exhibited moderate inhibitory effects against NO production in lipopolysaccharide-stimulated RAW 264.7 cells (IC50 values of 13.74 mu M and 13.92 mu M, respectively). In addition, 1 and 7 showed significant anti-inflammatory activities against the production of TNF-alpha, IL-1 beta, IL-6 and COX-2. Western blot analysis was further performed to reveal the mechanism of anti-inflammatory action via inhibition of the NF-kappa B activation.