St. John's Wort Extract Ze 117 (Hypericum perforatum) Inhibits Norepinephrine and Serotonin Uptake into Rat Brain Slices and Reduces β-Adrenoceptor Numbers on Cultured Rat Brain Cells

Abstract

Despite almost forty years of widespread use, the mode of action of antidepressant drugs is still largely unknown. There is agreement that these drugs interact with central neurotransmission. Common findings are acute inhibitory actions on reuptake mechanisms for norepinephrine (NE) and for serotonin (5-HT) at presynaptic axons and chronic adaptive effects on neurotransmitter receptors on postsynaptic membranes. In particular, beta-adrenoceptor downregulation has been observed after chronic treatment with most antidepressants in vivo and in cell culture systems. We studied the effectiveness of Ze 117 (St. John's wort) extract (Hypericum perforatum) on NE- and 5-HT-uptake into rat brain slices. Potency and efficacy of the Ze 117 extract were compared with those of tricyclic (TCA) and selective serotonin reuptake inhibitor (SSRI)-type antidepressants. A dose-dependent inhibition was seen on NE and 5-HT uptake into brain slices. The Ze 117 extract was more selective for the uptake of NE than for that of 5-HT. The maximal extent of uptake 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 confluent C6-cell cultures to Ze 117 extract resulted in a dose-dependent beta-adrenoceptor 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 extract Ze 117 contains active, but as yet unknown antidepressant principles with effects comparable to those of TCAs.

Molecular and Biochemical Characterization of an Enzyme Responsible for the Formation of Hypericin in St. John's Wort (Hypericum perforatum L.)

“…Similar drug dilution cases were observed with birth control pills and coronary transplant antirejection medications (5). Recent reports indicate some metabolites other than HyH as the cause of these unwanted drug interactions in St. John's wort extracts (5,9). Thus, the purification and bioprocessing of HyH, the antidepressant compound in St. John's wort, may be of medical importance in the treatment of depression, and in avoiding the side effects associated with this herbal remedy.…”

Antidepressant-induced Switch of β1-Adrenoceptor Trafficking as a Mechanism for Drug Action

“…Importantly, the onset of down-regulation and clinical effectiveness requires 10 -20 days of antidepressant treatment (43). We have previously shown that in cultured C6 cells chronic exposure to DMI results in a progressive reduction in ␤1AR surface receptor density within similar periods of time (10). C6 cells thus provide a valid model system to examine potential mechanisms that might underlie the clinical and experimental long term observations.…”

“…in cultured rat C6 glioblastoma cells (9,10). Thus, ␤AR down-regulation may directly result from postsynaptic actions of the antidepressants.…”

Hypericum-perforatum-Extrakt bei der Behandlung leichter bis mittelschwerer Depressionen Klinische und pharmakologische Aspekte

“…In der Studie von Kientsch et al [42] wurde außerdem eine b-down-Regulation in Astrozytenzellen der Ratte nach Gabe von ZE 117 nachgewiesen, die der b-down-Regulation nach Gabe von Desipramin vergleichbar war. Auch Müller et al [58] fanden eine Downregulation von b-Rezeptoren im Bereich des frontalen Kortex nach chronischer oraler Gabe von Hyperikumextrakten.…”