Anti-epileptic effects of valepotriate isolated from Valeriana jatamansi jones and its possible mechanisms

Objective: This work aimed to investigate the anti-epileptic effects of valepotriate isolated from Valeriana jatamansi Jones and studied its possible mechanisms. Methods: The anti-epileptic effects of valepotriate were studied using maximal electroshock-induced seizure (MES), pentylenetetrazole (PTZ)-induced epilepsy, and pentobarbital sodium-induced sleeping model in mice. The possible anti-epileptic mechanisms of valepotriate were investigated by analyzing the expressions of GABA A , GABA B , glutamic acid decarboxylase (GAD65), Bcl-2, and caspase-3 in the brain using Western blot assay. Results: The results indicated that valepotriate showed significant anti-epileptic activity against MES- and PTZ-induced epilepsy at doses of 5, 10, and 20 mg/kg, and ED 50 values for MES- and PTZ-induced epilepsy were 7.84 and 7.19 mg/kg, respectively. Furthermore, valepotriate (10 and 20 mg/kg) can significantly prolong sleeping time and shorten the latency time on the pentobarbital sodium-induced sleeping time test. Furthermore, valepotriate (5, 10, and 20 mg/kg) could significantly up-regulate the expression of GABA A , GAD65, and Bcl-2 and down-regulate the expression of caspase-3, but had no significant effect on the expression of GABA B . Conclusion: The results indicated that valepotriate had anti-epileptic activity and the mechanisms might be associated with regulation of GABA and inhibition of neuronal apoptosis.