Toxicology Laboratory, Faculty of Pharmacy, Illkirch, France.
Neurosci Res. 2010 Dec;68(4):337-44. doi: 10.1016/j.neures.2010.08.011. Epub 2010 Sep 15.
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.
α-细辛脑在三种不同毒性剂量的小鼠中表现出抗惊厥作用。100mg/kg 剂量降低了跑步机性能和运动活性，导致体温过低，并增强戊巴比妥诱导的睡眠。在 60mg/kg 和 22mg/kg 时分别观察到最后两种效应和无毒性。在化学（戊四氮、苦毒蕈碱、N-甲基-D-天冬氨酸、毛果芸香碱）和电（最大电休克）惊厥测试中，60mg/kg α-细辛脑既不能预防惊厥，也不能预防死亡，然而，它表现出保护样作用（延迟阵挛性和/或强直性惊厥的发作和/或小鼠死亡）。镁缺乏依赖性听觉性惊厥对非毒性剂量的 α-细辛脑（60mg/kg 及以下）有反应：22mg/kg 保护 50%的测试动物。由于这些惊厥对抗惊厥和抗氧化化合物都有反应，因此研究了 α-细辛脑的抗氧化特性，表明每毫克 α-细辛脑具有 5 个单位的超氧化物歧化酶样活性。用 α-细辛脑（7 天内每天 100mg/kg 的剂量）处理小鼠可诱导纹状体和海马中的脑抗氧化酶（超氧化物歧化酶、谷胱甘肽过氧化物酶和还原酶），在皮质中的诱导程度较小。鉴于最近关于慢性炎症/氧化应激在人类癫痫发病机制中的有害作用的发现，提出了 α-细辛脑的抗氧化和诱导特性是传统临床疗效的合理基础。
