New polycyclic polyprenylated acylphloroglucinols with antidepressant activities from Hypericum perforatum L.

Six new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperidiones A-F (1-6), were obtained from Hypericum perforatum L. Their structures were characterized via extensive spectroscopic analyses, the circular dichroism data of the in situ formed [Mo(OCOCH)] complexes, the nuclear magnetic resonance calculation with DP4 probability analysis, and the calculated electronic circular dichroism (ECD) spectra. Compounds 1-6 are bicyclic polyprenylated acylphloroglucinols with a major bicyclo[3.3.1]nonane-2,4,9-trione skeleton. Notably, compound 1 is a rare PPAP with a hydroperoxy group, and a plausible biosynthetic pathway for 1 was proposed. Compounds 4 and 6 exhibited significant neuroprotective effects under 10 μM against corticosterone (CORT)-injured SH-SY5Y cells. Furthermore, compound 4 demonstrated a noteworthy antidepressant effect at the dose of 5 mg/kg in the tail suspension test (TST) of mice, which was equivalent to 5 mg/kg of fluoxetine. And it potentially exerted an antidepressant effect through the hypothalamic-pituitary-adrenal (HPA) axis.