Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 164, Issue 5, Pages 1534-1546Publisher
WILEY
DOI: 10.1111/j.1476-5381.2011.01456.x
Keywords
EEG; epileptiform activity; flumazenil; GABA; magnolol; pentylenetetrazol; seizure
Categories
Funding
- National Natural Science Foundation of China [30625021, J0730860, 30770672, 30821002, 30970955, 30901797, 31070957]
- Shanghai Committee of Science and Technology [06PJ14008, 09PJ1401800, 09JC1402500, 10XD1400400, 10441901600]
- National Basic Research Program of China [2009CB5220004, 2011CB711000]
- Shanghai Leading Academic Discipline Project [B119]
- Ph.D. Programs Foundation of Ministry of Education of China [20070246186]
- China National Science and Technology Major Project for Drug Discovery [2009ZX09303-006]
- Program of Basic and Applied Researches for Innovations in Bio-oriented Industry of Japan
- Grants-in-Aid for Scientific Research [21500313] Funding Source: KAKEN
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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-beta-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 Mg2+-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.
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