Neurochemical studies with St. John's wort in vitro

The effect of extracts and constituents of St. John's wort, Hypericum perfo ratum, at various CNS receptors were studied by radioligand binding techniq ues in order to determine a profile of pharmacological activity in vitro. B inding inhibition was examined for the G-protein coupled opioid, serotonin (5-HT), histamine, neurokinin and corticotropin releasing factor (CRF) rece ptors, for the steroid estrogen-a receptor and for the ligand-gated ionchan nel GABA(A) receptor. Hypericin showed the most potent binding inhibition o f all tested constituents to human CRF1 receptor with an lC(50) value of 30 0 nM. Preliminary GTP gamma S-35 binding studies to CRF1 coupled G-protein indicated an antagonistic action for hypericin. The acylphloroglucinole hyp erforin failed to inhibit I-125-astressin binding to hCRF(1) receptor up to 10 muM. Hyperforin inhibited binding to opioid and serotonin (5-HT) recept ors at IC50 values between 0.4 and 3 muM while hypericin and pseudohyperici n inhibited with weaker potency. The biflavonoid 13,118-biapigenin inhibite d 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 like ly to be exclusively due to GABA present in the extract. We therefore hypot hesize that additive or synergistic actions of several ditsinct compounds m ay be responsible for the beneficial antidepressant effect of St. John's wo rt.