St. John's wort extract Ze 117 (Hypericum perforatum) inhibits norepinephrine and serotonin uptake into rat brain slices and reduces beta-adrenoceptor numbers on cultured rat brain cells

Despite almost forty years of widespread use, the mode of action of antidep ressant drugs is still largely unknown. There is agreement that these drugs interact with central neurotransmission. Common findings are acute inhibit ory actions on reuptake mechanisms for norepinephrine (NE) and for serotoni n (5-HT) at presynaptic axons and chronic adaptive effects on neurotransmit ter receptors on postsynaptic membranes. In particular, beta -adrenoceptor downregulation has been observed after chronic treatment with most antidepr essants in vivo and in cell culture systems. We studied the effectiveness o f Ze 117 (St. John's wort) extract (Hypericum perforatum) on NE- and 5-HT-u ptake into rat brain slices. Potency and efficacy of the Ze 117 extract wer e compared with those of tricyclic (TCA) and selective serotonin reuptake i nhibitor (SSRI)-type antidepressants. A dose-dependent inhibition was seen on NE and 5-HT uptake into brain slices, The Ze 117 extract was more select ive for the uptake of NE than for that of 5-HT. The maximal extent of uptak e inhibition by Ze 117 extract was comparable to that of imipramine (IMI), desipramine (DMI) or fluvoxamine for 5-HT, but lower for NE transport, than that of the synthetic antidepressants. Chronic exposure (8 days) of conflu ent C6-cell cultures to Ze 117 extract resulted in a close-dependent P-adre noceptor downregulation equal to that induced by DMI, a potent TCA. None of these effects could be achieved with either hypericin or hyperforin alone in a relevant dose range. Our results indicate that the St. John's wort ext ract Ze 117 contains active, but as yet unknown antidepressant principles w ith effects comparable to those of TCAs.