Evidence that total extract of Hypericum perforatum affects exploratory behavior and exerts anxiolytic effects in rats.
Clinical trials have extensively reported the ability of Hypericum perforatum extracts to exert a significant antidepressant activity. Hypericin, the main constituent of H. perforatum extract, is no more regarded as the active principle of the antidepressant activity of the drug. Hence, the question of which constituents are involved in the basic activity of the total extract, is still waiting for an answer. In the present study we focused our attention on the potential anxiolytic activity of H. perforatum total extract, and of some pure components such as protohypericin and a fraction containing hypericin and pseudohypericin. Herein we report that the total extract of H. perforatum increases the locomotor activity in the open field and exerts anxiolytic activity in the light-dark test, whereas the single components did not show any effect. Interestingly, the anxiolytic activity of the total extract was blocked by pretreatment of rats with the benzodiazepine antagonist Flumazenil, hence suggesting an implication of benzodiazepine receptor activation in the anxiolytic effect of H. perforatum extract. Electrophysiological studies, performed to gain more information on the mechanism of action, showed that hypericin reduced the GABA-activated chloride currents, while pseudohypericin did an opposite effect. Furthermore, both hypericin and pseudohypericin inhibited the activation of NMDA receptors.
Vandenbogaerde
A
A
Laboratorium voor Farmaceutische Biologie & Fytofarmacologie, Faculteit Farmaceutische Wetenschappen, K.U.Leuven, Van Evenstraat 4, B-3000, Leuven, Belgium.
Zanoli
P
P
Puia
G
G
Truzzi
C
C
Kamuhabwa
A
A
De Witte
P
P
Merlevede
W
W
Baraldi
M
M
D000818:Animals; D000873:Anthracenes; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects; D004594:Electrophysiology; D005106:Exploratory Behavior / Q000187:drug effects*; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D020902:Hypericum / Q000737:chemistry*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010569:Perylene / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000494:pharmacology; D010936:Plant Extracts / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010946:Plants, Medicinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
D000873:Anthracenes; D014151:Anti-Anxiety Agents; D018757:GABA Modulators; D058787:GABA-A Receptor Antagonists; D010936:Plant Extracts; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D005442:Flumazenil; C108325:protohypericin; D010569:Perylene; C004965:hypericin; C056602:pseudohypericin