Br J Pharmacol. 2011 Apr 26. doi: 10.1111/j.1476-5381.2011.01456.x. [Epub ahead of print]
Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, exerts anti-epileptic effects via GABA-benzodiazepine receptor complex in mice.
Chen C, Tan R, Qu W, Wu Z, Wang Y, Urade Y, Huang Z.
Department of Pharmacology; State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Institute of Brain Science, Fudan University, Shanghai, 200032, China; Department of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan.
Background: The aim of this study was to evaluate the anti-seizure effect of magnolol (6, 6', 7, 12-Tetramethoxy-2, 2'-dimethyl-1-beta-berbaman, C(18) H(18) O(2) ) and mechanisms involved. Experimental approach: Mice were treated with magnolol (20, 40 and 80 mg/kg) 30 min before the injection with pentylenetetrazol (PTZ, 60 mg/kg, i.p). The anti-seizure effects of magnolol were analyzed using seizure models of behaviour, electroencephalographic (EEG) and in vitro electrophysiology, and c-Fos expression in the hippocampus and cortex. Key results: Magnolol at doses of 40 and 80 mg/kg significantly delayed the onset of myoclonic jerks and generalized clonic seizures, and decreased the seizure stage and mortality compared with those of the vehicle-treated animals. EEG recordings showed that magnolol at 40, 80 mg/kg prolonged the latency of seizure onset and decreased the number of seizure spikes. The anti-epileptic effect of magnolol was reversed by the GABA(A) /benzodiazepine receptor antagonist flumazenil. Pretreatment with flumazenil decreased the effects of magnolol on prolongation of seizure latency and decline of seizure stage. In a Mg(2+) -free model of epileptiform activity via multi-electrode array recordings in mouse hippocampal slices, magnolol decreased spontaneous epileptiform discharges. Magnolol also significantly decreased seizure-induced Fos immunoreactivity in the piriform cortex, dentate gyrus, and hippocampal area CA1. These effects were attenuated by pretreatment with flumazenil. Conclusions and implications: These findings indicate that the inhibitory effects of magnolol on the epileptiform activity were mediated by the GABA(A) /benzodiazepine receptor complex.
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.