The Study On Anticonvulsant Effects Of Swertiamarin And Its Mechanism Involved In BDNF/ERK/CREB

OBJECTIVE:Epilepsy is defined as a common and major brain disorder,and one-third of individuals still experience seizures that do not respond to medication.Swertaimarin（SWE）was found to possess extracellular signal-regulated kinase（ERK）protein modulatory effect.In this study,we investigate the anticonvulsant and neuroprotective effects of SWE against Pilocarpine（PILO）Induced epileptic seizures.MATERIALS AND METHODS:Thirty minutes prior to the Pilocarpine（PILO）injection,the mice were administrated with SWE once.We observed seizure activity and electroencephalography（EEG）after the PILO injection,and mice were killed for Nissl,NEUN,TUNEL staining at 72 h after convulsion or SE onset.The expression of the Bax,Bcl-2,caspase-3,Brain Derived Neurotrophic Factor（BDNF）,Tyrosine kinase B（TrkB）,extracellular signal-regulated kinase（ERK）and cAMP response element-binding protein（CREB）was also evaluated in the hippocampus region of the brain by using western blot and q-PCR at 72 h after convulsion or SE onset.RESULTS:1.Anticonvulsant effects of swertiamarin on pilocarpine-induced epileptic mice.Compared with the model group,SWE（150,450 mg/kg）treatment significantly prolonged the latency of epilepsy（p<0.05,p<0.01）and the time to enter the status epilepticus（p<0.05,p<0.01）;compared with the model group,SWE administration（150,450 mg/kg）significantly reduced the rate of mice entering the status epilepticus and the mortality of mice（p<0.05,p<0.01）;compared with the model group,swertiamarin（150,450 mg/kg）treatment significantly reduced the average amplitude and total power of EEG（p<0.05,p<0.01）;SWE（150,450 mg/kg）treatment group and pilocarpine model group can alleviate pilocarpine-induced epilepsy induced hippocampus CA₁,CA₃ pathological damage.2.The neuroprotective effects of swertiamarin on pilocarpine-induced epileptic mice and the relationship between BDNF/ERK/CREB signaling pathway.Compared with the model group,SWE administration（450 mg/kg）decreased the expression of BDNF,p-ERK,CREB,p-CREB,Bax and caspase-3 protein in the hippocampus（p<0.05）;and significantly increased the expression of Bcl-2 protein（p<0.05）;compared with the model group,Swertiamarin（450 mg/kg）inhibited the expression of BDNF mRNA,Trkb mRNA,ERK mRNA,CREB mRNA,Bax mRNA and caspase-3 mRNA in the hippocampus（p<0.05）;and significantly upregulated the expression of Bcl-2 mRNA（p<0.05）.CONCLUSION:The findings of this study indicated that SWE exerts anticonvulsant and neuroprotective effects;Its mechanism may be related to SWE regulation of BDNF/ERK/CREB signaling pathway in the brain of epileptic mice.