柴胡皂苷 a 通过抑制 mTOR 信号通路在戊四氮诱导的大鼠中发挥抗癫痫作用。
Saikosaponin a functions as anti-epileptic effect in pentylenetetrazol induced rats through inhibiting mTOR signaling pathway.
机构信息
Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Soochow 215006, China.
Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Soochow 215006, China.
出版信息
Biomed Pharmacother. 2016 Jul;81:281-287. doi: 10.1016/j.biopha.2016.04.012. Epub 2016 Apr 22.
OBJECTIVE
Saikosaponin a (SSa), which is one major bioactive compound isolated from radix bupleuri, has been demonstrated to exhibit the properties of anticonvulsant and antiepileptic in few reports. This study aims to clarify the molecular mechanism by which SSa protects against pentylenetetrazol (PTZ) induced epileptic seizure.
METHODS
PTZ induced rat and hippocampal neuron were established. Treated rats or hippocampal neuron with SSa, and mTOR, P70S6K, IL-1β and TNF-α were then determined.
RESULTS
In PTZ induced rat, SSa significantly reduced seizure severity and duration while markedly elevated seizure latency, and it also down-regulated hippocampal p-mTOR, p-70S6K, L-1β and TNF-α expression. In hippocampal neurons exposed to PTZ, p-mTOR and p-70S6K expression levels were also decreased by SSa. Pre-incubated hippocampal neurons with leucine, an mTOR agonist, reversed the effects of SSa on decreasing cytokines expression and inhibiting cell apoptosis. The treatment of mTOR inhibitor rapamycin prevented against the increase of cytokines expression and hippocampal neuron apoptosis induced by PTZ. Leucine also canceled the alleviation of seizures and induction of hippocampal caspase-3 activity in PTZ induced rat with the treatment of SSa.
CONCLUSION
SSa protects against PTZ induced epileptic seizure and hippocampal neuron apoptosis through inhibiting mTOR signaling pathway.
目的
柴胡皂苷 a（SSa）是从柴胡中分离得到的一种主要生物活性化合物，已有研究表明其具有抗惊厥和抗癫痫作用。本研究旨在阐明 SSa 对抗戊四氮（PTZ）诱导的癫痫发作的分子机制。
方法
建立了 PTZ 诱导的大鼠和海马神经元模型。用 SSa 处理大鼠或海马神经元，然后测定 mTOR、P70S6K、IL-1β 和 TNF-α。
结果
在 PTZ 诱导的大鼠中，SSa 显著降低了癫痫发作的严重程度和持续时间，显著延长了癫痫发作潜伏期，同时还降低了海马 p-mTOR、p-70S6K、L-1β 和 TNF-α 的表达。在暴露于 PTZ 的海马神经元中，SSa 也降低了 p-mTOR 和 p-70S6K 的表达水平。用 mTOR 激动剂亮氨酸预先孵育海马神经元，可逆转 SSa 降低细胞因子表达和抑制细胞凋亡的作用。mTOR 抑制剂 rapamycin 的处理可防止 PTZ 诱导的细胞因子表达增加和海马神经元凋亡。亮氨酸还消除了 SSa 对 PTZ 诱导的大鼠癫痫发作的缓解和海马 caspase-3 活性的诱导作用。
结论
SSa 通过抑制 mTOR 信号通路，对 PTZ 诱导的癫痫发作和海马神经元凋亡具有保护作用。
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