In vitro binding studies with two Hypericum perforatum extracts - Hyperforin, hypericin and biapigenin - On 5-HT6, 5-HT7, GABA(A)/benzodiazepine, sigma, NPY-Y-1/Y-2 receptors and dopamine transporters

Interactions between neurotransmitter receptors involved in the pathophysio logy of depression, anxiety and ethanol consumption and two extracts (hydro methanolic and lipophilic extracts obtained with hypercritical CO2) from Hy pericum Perforatum L or St. John's wort (SJW) and three constituents (hyper forin, hypericin and biapigenin) were evaluated by in vitro binding assays. The two extracts, tested at 10 mug/ml, did not inhibit ligand binding at t he following receptors: serotonin 5-HT6 and 5-HT7, benzodiazepine, sigma an d neuropeptide Y (NPY) Y-1 and Y-2 receptors. The hydromethanolic extract, but not the lipophilic extract, interacted with GABA(A) receptors (IC50 5.5 mug/ml), while both interacted with the dopamine (DA) transporters, albeit with high IC50 values (24.5 and 12.9 mug/ml, respectively). Biapigenin (1 mug/ml, 2 muM) inhibited ligand binding at benzodiazepine receptors only (I C50: 2 muM). Hyperforin (1 mug/ml, 2 muM) only inhibited [H-3]WIN-35,428 bi nding to DA transporters, although the IC50 (5 muM) was higher than the IC5 0 found for inhibition of the synaptosomal DA reuptake (0.8 muM). This find ing extended the same observation previously described for the 5-HTergic sy stem to the DAergic system, confirming that the inhibition of monoamine reu ptake is due to a different mechanism than that of synthetic antidepressant s. Hypericin showed micromolar affinities for both NPY-Y-1 and Y-2 receptor s and for sigma receptors (IC50 3 - 4 muM). These hypericin activities migh t be of interest because NPY and sigma receptors have been associated with anxiety disorders, depressive illnesses and ethanol consumption. However, t hey were present at relatively high hypericin concentrations, and were also light-dependent (i.e. the IC50 values increased when binding assays were c arried out in the dark). Thus, our in vitro binding results may suggest tha t either the pharmacological effects of SJW are due to other molecules than hypericin or hyperforin (other constituents or active metabolites), or tha t the mechanism of action is different from those that have been considered up to now.