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Br J Pharmacol. 2011 Nov;164(5):1534-46. doi: 10.1111/j.1476-5381.2011.01456.x.

Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, exerts antiepileptic effects via the GABA/benzodiazepine receptor complex in mice.

Author information

1
Department of Pharmacology, Shanghai Medical College, Fudan University, Shanghai, China.

Abstract

BACKGROUND AND PURPOSE:

The aim of this study was to evaluate the anti-convulsant effects of magnolol (6, 6', 7, 12-tetramethoxy-2, 2'-dimethyl-1-β-berbaman, C18H18O2) and the mechanisms involved.

EXPERIMENTAL APPROACH:

Mice were treated with magnolol (20, 40 and 80 mg·kg(-1)) 30 min before injection with pentylenetetrazol (PTZ, 60 mg·kg(-1), i.p.). The anti-seizure effects of magnolol were analysed using seizure models of behaviour, 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(-1) 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 (40 and 80 mg·kg(-1)) 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, using 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 epileptiform activity were mediated by the GABA(A) /benzodiazepine receptor complex.

PMID:
21518336
PMCID:
PMC3221106
DOI:
10.1111/j.1476-5381.2011.01456.x
[Indexed for MEDLINE]
Free PMC Article

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