Hyjapones A−D, trimethylated acyphloroglucinol meroterpenoids from Hypericum japonicum thunb. With anti-inflammatory activity

Four undescribed trimethylated acylphloroglucinol meroterpenoids, hyjapones A−D, along with seven known analogues, were isolated from Hypericum japonicum Thunb. Hyjapone A represents the first example of a double norflavesones-caryophyllene hybrid featuring a rare 6/6/9/4/6/6 hexacyclic frame. Hyjapone D was isolated as a natural product for the first time. Their structures and absolute configurations were established by comprehensive spectroscopic data analyses and electronic circular dichroism (ECD) calculations. The anti-inflammatory activities of all compounds were evaluated using lipopolysaccharide-induced RAW264.7 cells. Hyperjapone A showed more pronounced anti-inflammatory effect through reducing the production of nitric oxide (IC50 value of 11.32 ± 2.10 μM) and proinflammatory cytokines. In addition, the mechanistic studies revealed hyperjapone A inhibited LPS-induced activation of nuclear factor-κB.