Antiepileptic activity of total triterpenes isolated from Poria cocos is mediated by suppression of aspartic and glutamic acids in the brain

Context: Triterpenes from Poria cocos Wolf (Polyporaceae) have been used to treat various diseases in traditional Chinese medicine. However, the antiepileptic effects and mechanism are not fully understood.Objective: The objective of this study is to investigate the antiepileptic properties of total triterpenes (TTP) from the whole P. cocos.Materials and methods: The ethanol extract TTP was identified by HPLC fingerprint analysis. Male ICR mice were gavaged (i.g.) with TTP (5, 20, 80 or 160mg/kg) or reference drugs twice a day for 7 d. Antiepileptic activities of TTP were evaluated by maximal electroshock (MES)- and pentylenetetrazole (PTZ)-induced seizures in mice for 30 and 60min, respectively. Locomotor activity and Rota-rod tests were performed for 60min and 5min, respectively. The levels of glutamic acid (Glu), aspartic acid (Asp), -aminobutyric acid (GABA) and glycine (Gly) in convulsive mice were estimated. The chronic epileptic model of Wistar rats was built to measure expressions of glutamate decarboxylase 65 (GAD65) and GABA(A) in rat brain after TTP treatment.Results: The LC50 of TTP (i.g.) was above 6g/kg. TTP (5-160mg/kg) protected mice against MES- and PTZ-induced convulsions at 65.0% and 62.5%, respectively, but have no effect on rota-rod treadmill; TTP (20-160mg/kg) significantly reduced the locomotor activities, shortened the onset of pentobarbital sodium-induced sleep; TTP decreased Glu and Asp levels in convulsive mice, but increased the GAD65 and GABA(A) expressions in chronic epileptic rats at doses usage.Discussion and conclusion: TTP extracted from P. cocos possessed potential antiepileptic properties and is a candidate for further antiepileptic drug development.