Alpha-asarone from Acorus gramineus alleviates epilepsy by modulating A-Type GABA receptors
Alpha-asarone from Acorus gramineus alleviates epilepsy by modulating A-Type GABA receptors
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石菖蒲中的 α-细辛脑通过调节 A 型 GABA 受体缓解癫痫
DOI：
10.1016/j.neuropharm.2012.09.001
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发表时间：
2013-02-01
影响因子：
4.7
通讯作者：
Li, Yong
中科院分区：
文献类型：
--
作者：
Huang, Chen;Li, Wei-Guang;Li, Yong
α(α)-细辛醚是从中草药石菖蒲中分离得到的一种主要有效化合物，作为抗癫痫药物在临床上得到了广泛的应用，但其作用机制尚不清楚。在本研究中，我们研究了α-细辛脑对培养的大鼠海马神经元兴奋性的影响以及对戊四氮或海人藻酸盐致癫痫作用的影响。在细胞附着构型下，α-细辛醚抑制自发放电的放电频率，而在无镁溶液中维持这种放电频率。在全细胞构型下，α-细辛脑以浓度依赖的方式诱发内向电流，其EC50为248+/-33mU M，该作用可被GABA(A)受体阻断剂微球毒素和竞争性GABA(A)受体拮抗剂荷包牡丹碱所抑制，但不能被甘氨酸受体特异性阻断剂士的宁所抑制。强直的GABA电流和微小的自发抑制性突触后电流的测量表明，α-细辛醚增强了强直的GABA能抑制，而左相的GABA能抑制不受影响。在戊四氮和海人酸惊厥模型中，α-细辛醚通过延长小鼠阵挛发作和强直发作的潜伏期，降低小鼠的死亡率和体内癫痫发作的敏感性，从而抑制小鼠的癫痫活动，这可能依赖于GABA(A)受体的激活。综上所述，我们的结果提示，α-细辛脑通过增强紧张性GABA能抑制作用而抑制海马神经元的活动，从而在中枢神经系统产生抗癫痫作用。(C)2012爱思唯尔有限公司。保留所有权利。
Alpha (alpha)-asarone is a major effective compound isolated from the Chinese medicinal herb Acorus gramineus, which is widely used in clinical practice as an antiepileptic drug; however, its mechanism of action remains unclear. In this study, we have characterized the action of alpha-asarone on the excitability of rat hippocampal neurons in culture and on the epileptic activity induced by pentylenetetrazole or kainate injection in vivo. Under cell-attached configuration, the firing rate of spontaneous spiking was inhibited by application of alpha-asarone, which was maintained in the Mg2+-free solution. Under whole-cell configuration, alpha-asarone induced inward currents in a concentration-dependent manner with an EC50 of 248 +/- 33 mu M, which was inhibited by a GABA(A) receptor blocker picotoxin and a competitive GABA(A) receptor antagonist bicuculline but not a specific glycine receptor inhibitor strychnine. Measurement of tonic GABA currents and miniature spontaneous inhibitory postsynaptic currents indicated that alpha-asarone enhanced tonic GABAergic inhibition while left phasic GABAergic inhibition unaffected. In both pentylenetetrazole and kainate seizure models, alpha-asarone suppressed epileptic activity of mice by prolonging the latency to clonic and tonic seizures and reducing the mortality as well as the susceptibility to seizure in vivo presumably dependent on the activation of GABA(A) receptors. In summary, our results suggest that alpha-asarone inhibits the activity of hippocampal neurons and produces antiepileptic effect in central nervous system through enhancing tonic GABAergic inhibition. (C) 2012 Elsevier Ltd. All rights reserved.