Highly oxygenated guaiane-type sesquiterpene lactones from Artemisia sacrorum and their antihepatoma activity

The ethanol and EtOAc extracts of Artemisia sacrorum exhibited inhibitory effect against HepG2, Huh7, and SKHep-1 cell lines with inhibitory ratios of 65.5%, 28.1%, 84.6%, and 93.5%, 82.0%, 89.0% at 200 mu g/mL. Twentythree undescribed guaiane-type sesquiterpene lactones, artemisacrolides A-W, were isolated from A. sacrorum under the guidance of antihepatoma activity. Their structures were elucidated by spectral data (HRESIMS, IR, UV, 1D and 2D NMR), ECD calculations, and a single-crystal X-ray diffraction. Artemisacrolides A-U were guaiane-type sesquiterpene lactones possessing alpha-methylene-gamma-lactone and containing acetoxyl groups at C-8, and artemisacrolides V and W represented the first report from the genus Artemisia with a 1,10-rearranged guaianetype sesquiterpene lactone. Antihepatoma assay suggested that artemisacrolides A-U demonstrated better inhibitory activity in Huh7 and SK-Hep-1 cells than those of HepG2 cells. Among them, nine compounds exhibited significant inhibitory activity against Huh7 cells with IC50 values of 8.2-14.3 mu M, superior or equal to that of sorafenib; seven compounds demonstrated obvious activity against SK-Hep-1 cells with IC50 values of 13.5-19.2 mu M, which were equivalent to that of sorafenib. Artemisacrolides B and E were the most active ones in three human hepatoma cell lines with IC50 values of 21.9, 8.2, 16.9 and 22.6, 9.0, 17.3 mu M.