Neurochemical studies with St. John's wort in vitro

The effect of extracts and constituents of St. John's wort, Hypericum perforatum, at various CNS receptors were studied by radioligand binding techniques in order to determine a profile of pharmacological activity in vitro. Binding inhibition was examined for the G-protein coupled opioid, serotonin (5-HT), histamine, neurokinin and corticotropin releasing factor (CRF) receptors, for the steroid estrogen-a receptor and for the ligand-gated ionchannel GABA(A) receptor. Hypericin showed the most potent binding inhibition of all tested constituents to human CRF1 receptor with an lC(50) value of 300 nM. Preliminary GTP gamma S-35 binding studies to CRF1 coupled G-protein indicated an antagonistic action for hypericin. The acylphloroglucinole hyperforin failed to inhibit I-125-astressin binding to hCRF(1) receptor up to 10 muM. Hyperforin inhibited binding to opioid and serotonin (5-HT) receptors at IC50 values between 0.4 and 3 muM while hypericin and pseudohypericin inhibited with weaker potency. The biflavonoid 13,118-biapigenin inhibited H-3-estradiol binding to the estrogen-a receptor with an IC50 value of 1 muM. The inhibition of H-3-muscimol binding to the GABA(A) receptor is likely to be exclusively due to GABA present in the extract. We therefore hypothesize that additive or synergistic actions of several ditsinct compounds may be responsible for the beneficial antidepressant effect of St. John's wort.