Saikosaponin a functions as anti-epileptic effect in pentylenetetrazol induced rats through inhibiting mTOR signaling pathway

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-1 beta and TNF-alpha 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-1 beta and TNF-alpha 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. (C) 2016 Published by Elsevier Masson SAS.