The Primary Study Of Anticonvulsive Effect And Mechanism Of N-methyl-N-cis-styrly-cinnamamide

Objective:To investigate the anticonvulsant effect of the seed extract of Clausena lansium, N-methyl-N-cis-styryl-cinnamamide, and to explore its mechanism of anticonvulsive function. We want to provide basis for future research of the natural medicine.Materials and methods:Forty Sprague-Dawely rats were randomly divided into five groups with 8 rats in each group:normal control (20 mL/L Tween 80+Normal Saline), model control (20 mL/L Tween 80+Penicillin), positive control (Sodium Valproate 120 mg/kg+Penicillin), low dose treatment (s-MSC 75 mg/kg+Penicillin), high dose treatment (s-MSC 150 mg/kg+ Penicillin). The epilepsy rat model was established by localized intracortical injections of penicillin. The effects of pretreatments of the rats with N-methyl-N-cis-styryl-cinnamamide (intraperitoneal injection, ip) on the penicillin-induced seizure activities and the epileptiform discharges recorded by electrocorticogram (ECoG) were observed. The results were compared with the control groups. The change of intracellular calcium ion concentration (cell [Ca2+] i) in rats neure of the left side of the primary, secondary somatic motor cortex and left hippocampus was detected by flow cytometry.Results:(1) The penicillin-induced seizure was significantly lightened in both the pretreatment groups (75 and 150 mg/kg N-methyl-N-cis-styryl-cinnamamide), compared with the model group. N-methyl-N-cis-styryl-cinnamamide (75 and 150 mg/kg) could significantly prolonged the latency of epileptiform activities, shorten the duration of epileptiform discharges and decreased the mean spike frequency in the late stage (P<0.05 or P<0.01). However, there was no significant difference in the highest value or the lowest value of the epileptiform waves between the model and N-methyl-N-cis-styryl-cinnamamide treatment groups.(2) Sodium Valproate (120 mg/kg) could significantly inhibit the seizure activity and epileptiform discharges caused by penicillin-localized injections in the cortex of rats.(3) The neuronal intracellular calcium ion concentration (cell [Ca2+] i) of rat cerebral cortex was significantly increased after penicillin injection, compared with the normal control group (P>0.01). Compared with the model group, high dose N-methyl-N-cis-styryl-cinnamamide and Sodium Valproate could significantly decreased intracellular calcium ion concentration (cell [Ca2+] i) (P<0.01). However, there was no significant difference in intracellular calcium concentration (cell [Ca2+] i) between the model and low dose N-methyl-N-cis-styryl-cinnamamide treatment group.Conclusions:(1) The seed extract of Clausena lansium, N-methyl-N-cis-styryl-cinnamamide, can significantly inhibit the seizure and epileptiform discharges caused by penicillin-localized injections in the cortex of rats, suggesting that the natural substance has an anticonvulsive function.(2) The mechanism of s-MSC inhibiting the seizure model caused by penicillin-localized injections in the cortex of rats might relate with decreasing intracellular calcium ion concentration (cell [Ca2+] i) level.(3) In the epilepsy rats model established by localized intracortical injections of penicillin, the main epileptiform discharges in ECoGs are spike wave, spike and slow wave complex. The mechanism might relate with increasing the neuronal intracellular calcium ion content.(4) Sodium Valproate has a very significant anticonvulsive function in the seizure modle caused by penicillin-localized injections in the cortex of rats. The mechanism might relate with decreasing the neuronal intracellular calcium ion content. IV...