Extracts and constituents of Hypericum perforatum inhibit the binding of various ligands to recombinant receptors expressed with the Semliki forest virus system

Extracts, fractions and constituents of Hypericum perforatum were studied f or in vitro receptor binding with various ligands to recombinant CNS recept ors expressed with the Semliki Forest virus expression system. For this pur pose we have prepared membranes of CHO cells with high density of several o pioid, serotonin, estrogen, histamine, GABAA, neurokinin and metabotropic g lutamate receptors, respectively. A lipophilic Hypericum fraction revealed relatively potent inhibition to the binding of the mu-, delta- and kappa-op ioid and the 5-HT6 and 5-HT7 receptors. Moreover, Hypericum constituents su ch as the naphthodianthrones, hypericin and pseudohypericin, and the phloro glucinole hyperforin inhibited both binding to the opioid and serotonin rec eptors in the lower micromolar range. Estrogen binding was 50% inhibited by the biflavonoid I3,II8-biapigenin at micromolar concentration. The lipophi lic Hypericum fraction provided a less potent inhibition of the neurokinin- l receptor binding compared to the opioid and serotonin receptors. A total ethanolic Hypericum extract potently inhibited GABAA binding at approximate ly 3 mu g/ml. This inhibition is however not specific to Hypericum, since e xtracts of plants like Valeriana officinalis and Passiflora incarnata showe d similar inhibitions. Binding to neither histamine nor metabotropic glutam ate receptors was affected by Hypericum extracts. These results support the hypothesis that several active constituents of Hypericum might in a synerg istic way contribute to its antidepressant effect in the central nervous sy stem.