New sesquiterpenes and flavonoids from the fruits of Hypericum ascyron L. with nitric oxide inhibitory activities.

Seven previously undescribed compounds (1-7), including two norsesquiterpenes (1 and 3), one cadinane-type sesquiterpene (2), one flavonoid (4), and three xanthones (5-7), along with 17 known analogs (8-24), were isolated from the ethyl acetate extract from the fruits of Hypericum ascyron L. Four pairs of enantiomers (4a/4b, 5a/5b, 6a/6b and 7a/7b) were resolved from naturally scalemic mixtures by chiral HPLC. Their full structures were unambiguously established through comprehensive spectroscopic analyses, including 1D and 2D NMR, HR-ESI-MS, electronic circular dichroism (ECD) calculations, and DP4+ probability. Notably, 13 isolated compounds (1, 2, and 8-18) of them belong to five types of sesquiterpenes. The NO inhibitory activities of the isolated compounds were preliminarily evaluated in LPS-stimulated RAW264.7 cells. Compounds 3, 15, 18, 22, and 24 demonstrated moderate NO inhibitory effects, and compound 22 exhibited the strongest NO inhibitory effect among the tested compounds, with an IC50 value of 32.00 ± 1.54 μM, suggesting that it may warrant further investigation.