title: Activities of α-asarone in various animal seizure models and in biochemical assays might be essentially accounted for by antioxidant properties.
abstract: Anticonvulsant properties of α-asarone were studied in mice at three doses with different toxicity. The 100mg/kg dose decreased both treadmill performance and locomotor activity, caused hypothermia, and potentiated pentobarbital-induced sleep. The last two effects and no toxicity were observed at 60 and 22mg/kg, respectively. In chemical (pentylenetetrazole, picrotoxin, N-methyl-D-aspartate, pilocarpine) and electrical (maximal electroshock) seizure tests, neither seizures nor death were prevented by 60 mg/kg α-asarone which, however, exhibited protective-like effects (delay in the onset of clonic and/or tonic seizures and/or in the death of mice). Magnesium deficiency-dependent audiogenic seizures responded to non-toxic doses of α-asarone (60 mg/kg and less): 22 mg/kg protecting 50% of tested animals. Because these seizures respond to both anti-seizure and antioxidant compounds, antioxidant properties of α-asarone were studied, indicating 5 Units of superoxide dismutase-like activity per mg α-asarone. Treatment of mice by α-asarone (daily dose of 100mg/kg during 7 days) induced brain antioxidant enzymes (superoxide dismutase, glutathione peroxidase and reductase) in striatum and hippocampus and to a lesser extent in cortex. In view of recent findings about deleterious roles of chronic inflammatory/oxidant stresses in human epilepsy outcome, antioxidant and inductive properties of α-asarone are proposed to be coherent bases for traditional clinical efficacy.
authors.affiliation: Toxicology Laboratory, Faculty of Pharmacy, Illkirch, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Pages
authors.forename: Pierre
authors.initials: P
authors.lastname: Maurois
authors.forename: Bernadette
authors.initials: B
authors.lastname: Delplanque
authors.forename: Pierre
authors.initials: P
authors.lastname: Bac
authors.forename: James P
authors.initials: JP
authors.lastname: Stables
authors.forename: Joaquín
authors.initials: J
authors.lastname: Tamariz
authors.forename: Germán
authors.initials: G
authors.lastname: Chamorro
authors.forename: Joseph
authors.initials: J
authors.lastname: Vamecq
mesh_terms: D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005979:Glutathione Peroxidase / Q000096:biosynthesis; D005980:Glutathione Reductase / Q000096:biosynthesis; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D012640:Seizures / Q000188:drug therapy* / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000096:biosynthesis
chemical_list: D000081248:Allylbenzene Derivatives; D000840:Anisoles; D000927:Anticonvulsants; D000975:Antioxidants; C012195:asarone; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase