Discovery of Bioactive Polycyclic Polyprenylated Acylphloroglucinol from Hypericum patulum that Protects Against Hepatic Ischemia/Reperfusion Injury

Hepatic ischemia/reperfusion injury (IRI) is one of the main causes of graft dysfunction after liver surgery. In the process of studying the active secondary metabolites from Hypericum patulum, five new homoadamantane type polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperhomanoons A–E (1–5), and one known congener, hypersampsone O (6), were obtained. Importantly, 6 exhibited significant activity protect the CoCl₂-induced hypoxia damage in hepatocytes, and in the vascular interruption-induced hepatic IRI murine model, pretreatment with 6 could effectively prevent liver damage and hepatocyte apoptosis. This is the first report disclosed that PPAPs as potential candidate against IRI and might underscore the PPAP-type metabolites as promising lead compounds for designing novel agents fight IRI related diseases.