Bioactive prenylated acylphloroglucinols from Hypericum scabrum

Ten prenylated acylphloroglucinols were obtained from the whole herb of Hypericum scabrum, four of which (1-4) are undescribed compounds. Structural identification was accomplished by extensive spectral analyses including HRESIMS, 1D and 2D NMR, DP4+ combined with ¹³C NMR quantum calculation as well as ECD simulation. Subsequent cytotoxic and neuroprotective activity assays revealed that all compounds except 4, 8, and 9 exhibited moderate cytotoxicity against Cal-27 cells, with compound 1 displaying the strongest activity (IC₅₀ = 21.29 ± 0.03 µM). At varying concentrations, all tested compounds exerted certain protective effects against corticosterone-induced damage to PC12 cells, with compound 9 showing the strongest protective activity. These findings underscore the dual cytotoxic and neuroprotective potential of prenylated acylphloroglucinols from H. scabrum, highlighting their promise as candidates for human health and therapeutic development.