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氰基香芹酮的抗惊厥和抗氧化作用及其对小鼠海马乙酰胆碱酯酶活性的影响。

Anticonvulsant and antioxidant effects of cyano-carvone and its action on acetylcholinesterase activity in mice hippocampus.

机构信息

Laboratory of Research in Experimental Neurochemistry of Post-Graduation Program in Pharmaceutics Science, Federal University of Piauí, Teresina, Piauí, Brazil.

出版信息

Cell Mol Neurobiol. 2012 May;32(4):633-40. doi: 10.1007/s10571-012-9812-8. Epub 2012 Feb 29.

Abstract

The anticonvulsant effect of cyano-carvone, a monoterpene monocyclic, was investigated in epilepsy model induced by pilocarpine. Cyano-carvone at doses of 25, 50 or 75 mg/kg promoted a reduction of 16.7, 33 and 66.7%, respectively, against pilocarpine-induced seizures, and it was efficacious in increasing both the latency to first seizures and the survival percentage, resulting in 33.3, 67 and 91.7% of protection against death induced by seizures, respectively (P < 0.05). The reference drug atropine (25 mg/kg) also produced a significant protection (100%). Its monoterpene, at 25, 50 and 75 mg/kg, was also capable to increase the latency for installation of status epilepticus induced by pilocarpine, and presented a significant protection against lipid peroxidation and nitrite formation in mice hippocampus (P < 0.05). In addition, it was observed that the cyano-carvone pretreatment increased the acetylcholinesterase activity in mice hippocampus after pilocarpine-induced seizures. The present results clearly indicate the anticonvulsant ability of cyano-carvone, which can be, at least in part, explained by the increased activity of the acetylcholinesterase enzyme. Our data suggest that the action mechanism can also be due to a direct activation of the antioxidant enzymes that could be associated with a reduction observed in oxidative stress in mice hippocampus, probably involving an inhibition of free radical production.

摘要

氰基香芹酮,一种单萜单环化合物,在匹鲁卡品诱导的癫痫模型中被研究了其抗惊厥作用。氰基香芹酮在剂量为 25、50 或 75mg/kg 时,分别对匹鲁卡品诱导的癫痫发作有 16.7%、33%和 66.7%的抑制作用,并且在增加首次癫痫发作的潜伏期和存活率方面都有效,导致对癫痫发作引起的死亡分别有 33.3%、67%和 91.7%的保护作用(P<0.05)。参考药物阿托品(25mg/kg)也产生了显著的保护作用(100%)。其单萜,在 25、50 和 75mg/kg 时,也能够增加由匹鲁卡品诱导的癫痫持续状态的潜伏期,并对小鼠海马中的脂质过氧化和亚硝酸盐形成有显著的保护作用(P<0.05)。此外,还观察到氰基香芹酮预处理能够增加匹鲁卡品诱导的癫痫发作后小鼠海马中的乙酰胆碱酯酶活性。这些结果清楚地表明了氰基香芹酮的抗惊厥能力,这至少可以部分解释为乙酰胆碱酯酶活性的增加。我们的数据表明,其作用机制也可能是由于抗氧化酶的直接激活,这可能与小鼠海马中氧化应激的降低有关,可能涉及自由基生成的抑制。

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