Bioassay and UPLC-Q-Orbitrap-MS/MS guided isolation of polycyclic polyprenylated acylphloroglucinols from St. John's wort and their neuroprotective activity

Abstract

St. John’s wort ( Hypericum perforatum L.) is a popular dietary supplement ingredient used for the treatment of mild-to-moderate depression in the United States and Germany. Reported studies mainly focused on the biological evaluation and mechanism study of its crude extracts or two main components (namely, hypericin and hyperforin). However, it is unclear whether other phytochemicals including polycyclic polyprenylated acylphloroglucinols (PPAPs) contributed to the neuroprotective effects of H. perforatum. Here, bioassay and ultra performance liquid chromatography–quadrupole orbitrap mass spectrometry (UPLC-Q-Orbitrap-MS/MS) guided isolation were applied to discover bioactive PPAPs from the crude extracts of H. perforatum. A new PPAP, named hyperforen A ( 2 ), along with nine known PPAPs ( 1 and 3 – 10 ), were identified from an ethyl acetate extract of H. perforatum . To the best of our knowledge, compound 2 represents the first PPAP with an unprecedented bicyclo[7.3.0]dodecane core. The chemical structures of the isolates were elucidated by extensive spectroscopic analysis and electronic circular dichroism calculations. Moreover, compounds 1 – 3 , 6 , and 10 (10 μM) exhibited significant neuroprotective effects against corticosterone-induced injury in PC12 cells. Fingings from the current study suggest that bioactive PPAPs from H. perforatum are promising compouds for the management of depression.