Withanolides from Datura stramonium: two unprecedented B-ring-seco derivatives and anti-inflammatory active analogues.

UV-guided separation of the Datura stramonium L. extract led to the elucidation of thirteen previously unreported withanolides (1-13), together with nine known analogues (14-22). Compounds 1 and 2 are unprecedented withanolides featuring B-ring cleavage and bearing two formyl (-CHO) groups. The structures of the new withanolides were elucidated on the basis of UV, HRESIMS, and NMR data. The inhibitory effects of the isolated compounds on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglial cells were evaluated. Compounds 16 and 22 exhibited potent in vitro anti-inflammatory activity with IC50 values ranging from 6.72 ± 0.08 to 7.48 ± 0.28 μM-superior to that of the positive control dexamethasone (DXMS) (IC50 = 8.04 ± 0.60 μM). These results suggest that the leaves of D. stramonium may represent a promising source of lead compounds for treating inflammation-related diseases.