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-α receptor and for the ligand-gated ionchannel GABA_A receptor. Hypericin showed the most potent binding inhibiton of all tested constituents to human CRF₁ receptor with an IC₅₀ value of 300 nM. Preliminary GTPγ³⁵S binding studies to CRF₁ coupled G-protein indicated an antagonistic action for hypericin. The acylphloroglucinole hyperforin failed to inhibit ¹²⁵I-astressin binding to hCRF₁ receptor up to 10 µM. Hyperforin inhibited binding to opioid and serotonin (5-HT) receptors at IC₅₀ values between 0.4 and 3 µM, while hypericin and pseudohypericin inhibited with weaker potency. The biflavonoid I3,II8-biapigenin inhibited ³H-estradiol binding to the estrogen-α receptor with an IC₅₀ value of 1 µM. The inhibition of ³H-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.

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