Prenylated flavonoids from Hypericum perforatum L. and their anti-neuroinflammatory and neuroprotective activities

Hypericum perforatum, widely cultivated in China for its substantial economic and medicinal advantages, is utilized in the pharmaceuticals, dietary supplements, and cosmetics industries. This study aimed to identify bioactive components with neuroprotective properties within the plant and to explore their underlying mechanisms. We isolated and identified seventeen compounds, including four novel ones (1−4) and thirteen known metabolites (5−17). The anti-neuroinflammatory and neuroprotective effects of these compounds were comprehensively assessed. Our results demonstrated that compounds 5, 6, and 9 effectively reduced nitric oxide (NO) release by inhibiting the expression of inducible nitric oxide synthase (iNOS), demonstrating notable anti-neuroinflammatory properties. Furthermore, compounds 4 and 5 were found to trigger the Nrf2/HO-1 pathway, indicating their considerable neuroprotective effects. Notably, the neuroprotective efficacy of the novel compound 4 was also preliminarily validated in a zebrafish model. These findings suggest that the prenylated flavonoids from H. perforatum may serve as potential neuroprotective agents for the prevention and treatment of neurodegenerative diseases.