Inhibition of benzodiazepine binding in vitro by amentoflavone, a constituent of various species of Hypericum.
Flower extracts of Hypericum perforatum, Hypericum hirsutum, Hypericum patulum and Hypericum olympicum efficiently inhibited binding of [3H]flumazenil to rat brain benzodiazepine binding sites of the GABAA-receptor in vitro with IC50 values of 6.83, 6.97, 13.2 and 6.14 micrograms/ml, respectively. Single constituents of the extracts like hypericin, the flavones quercetin and luteolin, the glycosylated flavonoides rutin, hyperoside and quercitrin and the biflavone 13, II8-biapigenin did not inhibit binding up to concentrations of 1 microM. In contrast, amentoflavone revealed an IC50 = 14.9 +/- 1.9 nM on benzodiazepine binding in vitro. Comparative HPLC analyses of hypericin and amentoflavone in extracts of different Hypericum species revealed a possible correlation between the amentoflavone concentration and the inhibition of flumazenil binding. For hypericin no such correlation was observed. Our experimental data demonstrate that amentoflavone, in contrast to hypericin, presents a very active compound with regard to the inhibition of [3H]-flumazenil binding in vitro and thus might be involved in the antidepressant effects of Hypericum perforatum extracts.
Baureithel
K H
KH
Dept. of Pharmaceutical Biology, University of Basel, Switzerland.
Büter
K B
KB
Engesser
A
A
Burkard
W
W
Schaffner
W
W
D000818:Animals; D000873:Anthracenes; D000928:Antidepressive Agents / Q000494:pharmacology*; D044946:Biflavonoids; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D005442:Flumazenil / Q000378:metabolism; D018757:GABA Modulators / Q000378:metabolism; D058787:GABA-A Receptor Antagonists; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D010946:Plants, Medicinal; D051381:Rats
D000873:Anthracenes; D000928:Antidepressive Agents; D044946:Biflavonoids; D005419:Flavonoids; D018757:GABA Modulators; D058787:GABA-A Receptor Antagonists; D010936:Plant Extracts; D005442:Flumazenil; D010569:Perylene; C004965:hypericin; C011164:amentoflavone