Activities of α-asarone in various animal seizure models and in biochemical assays might be essentially accounted for by antioxidant properties.
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.
Pages
Nicole
N
Toxicology Laboratory, Faculty of Pharmacy, Illkirch, France.
Maurois
Pierre
P
Delplanque
Bernadette
B
Bac
Pierre
P
Stables
James P
JP
Tamariz
Joaquín
J
Chamorro
Germán
G
Vamecq
Joseph
J
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
D000081248:Allylbenzene Derivatives; D000840:Anisoles; D000927:Anticonvulsants; D000975:Antioxidants; C012195:asarone; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase