Effects of Hypericum montbretti Extract on the Central Nervous System and Involvement of GABA (A)/Benzodiazepine Receptors in its Pharmacological Activity

Abstract

The present study was undertaken to investigate the putative activity of a methanol extract of Hypericum montbretti (Guttiferae) on the central nervous system. Rutin (1519 ppm) and quercitrin (784 ppm) were identified as the major phenolic compounds in the extract. When administered at 25, 50 and 100 mg/kg doses, the extract decreased the total number of head-dipping behaviours performed by mice during a hole-board test. Administration of both the extract and diazepam (2 mg/kg) reduced spontaneous locomotory activity, potentiated hexobarbital (60 mg/kg)-induced sleeping parameters and prevented pentylenetetrazole (80 mg/kg)-induced seizures relative to the controls. These findings are the first to indicate the sedative and anticonvulsant activities of H. montbretti extract. Atropine (2 mg/kg) and naloxone (5 mg/kg) pre-treatment did not reverse the sedative effect, indicating that muscarinic and opioidergic mechanisms did not contribute to the pharmacological action. However, pre-treatment with flumazenil (a benzodiazepine receptor antagonist) reversed both the sedative and anticonvulsant effects induced by a 100 mg/kg dose of the extract, indicating the involvement of the GABA(A)-benzodiazepine receptor complex. In conclusion, H. montbretti extract is a novel candidate as a sedative and anticonvulsant drug for the treatment of sleep disorders and for the prevention of epileptic seizures.