Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Science, Kunming, China.
Sci Rep. 2017 May 10;7(1):1701. doi: 10.1038/s41598-017-01734-z.
Epilepsy is one of the most common neurological disorders and the administration of antiepileptic drugs (AEDs) is the most common treatment. Although there are more than 15 AEDs available, a third of epilepsy patients remain refractory to available drugs, so novel effective drugs are needed. Here, we found that DV21, which is a natural triterpenoid compound extracted from plants of the Asclepiadaceae family, significantly decreased the incidence and stages of seizures in three classical drug-induced acute seizure models in C57BL/6 mice. Furthermore, we also found that the antiepileptic effect of DV21 might be partly mediated through reducing the excitability of cortical pyramidal neurons by increasing M current, which are low-threshold non-inactivating voltage-gated potassium currents. Moreover, the application of XE991, an inhibitor of M current, could block most the antiepileptic effect of DV21. Taken together, our results indicated that DV21 might be a novel leading compound for the treatment of epilepsy.
癫痫是最常见的神经障碍之一，抗癫痫药物（AEDs）的管理是最常见的治疗方法。尽管有超过 15 种 AED 可用，但仍有三分之一的癫痫患者对现有药物无反应，因此需要新的有效药物。在这里，我们发现 DV21，一种从夹竹桃科植物中提取的天然三萜类化合物，可显著降低 C57BL/6 小鼠三种经典药物诱导的急性癫痫模型中的癫痫发作发生率和阶段。此外，我们还发现，DV21 的抗癫痫作用可能部分通过增加 M 电流来降低皮质锥体神经元的兴奋性来介导，M 电流是一种低阈值非失活电压门控钾电流。此外，M 电流抑制剂 XE991 的应用可以阻断 DV21 的大部分抗癫痫作用。总之，我们的研究结果表明，DV21 可能是一种治疗癫痫的新型先导化合物。
