Activities of α-asarone in various animal seizure models and in biochemical assays might be essentially accounted for by antioxidant properties

• Published in: Neuroscience research 2010-12, Vol.68 (4), p.337-344
• Main Authors: Pages, Nicole, Maurois, Pierre, Delplanque, Bernadette, Bac, Pierre, Stables, James P., Tamariz, Joaquίn, Chamorro, Germán, Vamecq, Joseph
• Format: Article
• Language: English
• Subjects: Animals; Anisoles - pharmacology; Anticonvulsants - pharmacology; Antioxidant; Antioxidants - pharmacology; Audiogenic test; Brain - drug effects; Brain - metabolism; Disease Models, Animal; Electroshock; Epilepsy; Female; Glutathione Peroxidase - biosynthesis; Glutathione Reductase - biosynthesis; Magnesium deficiency; Mice; Motor Activity - drug effects; N-methyl- d-aspartate; Neuroprotection; Pentylenetetrazole; Picrotoxin; Pilocarpine; Seizure; Seizures - drug therapy; Seizures - metabolism; Superoxide Dismutase - biosynthesis; α-Asarone
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2010.08.011

Anticonvulsant properties of α-asarone were studied in mice at three doses with different toxicity. The 100 mg/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 22 mg/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 100 mg/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.