Inhibition of benzodiazepine binding in vitro by amentoflavone, a constituent of various species of Hypericum

• Published in: Pharmaceutica acta Helvetiae Vol. 72; no. 3; pp. 153 - 157
• Main Authors: H. Baureithel, Karl, Büter, Karin Berger, Engesser, Anja, Burkard, Willy, Schaffner, Willi
• Format: Journal Article
• Language: English
• Published: Switzerland Elsevier B.V 01.06.1997
• Subjects: [3H]flumazenil; Amentoflavone; Animals; Antidepressive Agents - pharmacology; Benzodiazepine receptor (BDZ-R); Biflavonoids; Binding, Competitive; Brain - drug effects; Brain - metabolism; Cells, Cultured; Flavonoids - isolation & purification; Flavonoids - pharmacology; Flumazenil - metabolism; GABA Modulators - metabolism; GABA-A Receptor Antagonists; Hypericum; Perylene - analogs & derivatives; Perylene - pharmacology; Plant Extracts - pharmacology; Plants, Medicinal; Rats; Amentoflavone; [3H]flumazenil; Hypericum; Benzodiazepine receptor (BDZ-R)
• DOI: 10.1016/S0031-6865(97)00002-2
• ISSN: 0031-6865

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 μg/ml, respectively. Single constituents of the extracts like hypericin, the flavones quercetin and luteolin, the glycosylated flavonoides rutin, hyperoside and quercitrin and the biflavone I3, II8-biapigenin did not inhibit binding up to concentrations of 1 μM. 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.