title: Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, exerts antiepileptic effects via the GABA/benzodiazepine receptor complex in mice.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  These findings indicate that the inhibitory effects of magnolol on epileptiform activity were mediated by the GABA(A) /benzodiazepine receptor complex.
authors.affiliation: Department of Pharmacology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: C R
authors.initials: CR
authors.lastname: Chen
authors.forename: R
authors.initials: R
authors.lastname: Tan
authors.forename: W M
authors.initials: WM
authors.lastname: Qu
authors.forename: Z
authors.initials: Z
authors.lastname: Wu
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Urade
authors.forename: Z L
authors.initials: ZL
authors.lastname: Huang
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D017705:Lignans / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D031566:Magnolia / Q000737:chemistry*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D024301:Plant Bark / Q000737:chemistry; D011963:Receptors, GABA-A / Q000378:metabolism*; D012640:Seizures / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D001713:Biphenyl Compounds; D017705:Lignans; D011963:Receptors, GABA-A; C005498:magnolol