Hyperhenrones: Prenylated α-pyrones with anti-inflammatory activity from Hypericum henryi

Fourteen previously undescribed α-pyrone derivatives (1–14) together with four known analogs (15–18) were isolated from a traditional Chinese medicinal plant Hypericum henryi. Compounds (+)/(−)-1, 2, and 3 share a rare 6/6/4/6/6 polycyclic skeleton. Compound 14 was the first example of a 7,7-dimethyl-pyran-4-one moiety. Their structures were elucidated using comprehensive spectroscopic analyses and electronic circular dichroism calculations. The anti-inflammatory activities of 1–18 were screened in lipopolysaccharide-induced RAW264.7 cells. Among them, compounds 14, (+)-18, and (−)-18 exhibited inhibitory effects against nitric oxide production in LPS-induced RAW264.7 cells. Additionally, compound 14 suppressed the expression of cyclooxygenase-2 and inducible nitric oxide synthase in LPS-induced RAW264.7 cells. Furthermore, preliminary mechanism studies indicated that compound 14 suppressed the phosphorylation and degradation of the inhibitor of NF-κB, and this led to the inhibition of NF-κB activation.