Effects of berberine pretreatment on degree and incubation period of epileptic seizure in mice with penicillin-induced epilepsy

LIU Zeye; XIANG Xuerui; FAN Mengmeng; XIANG Ting; FANG Chunyun; JIANG Ping

doi:10.3969/j.issn.1002-266X.2017.27.005

Abstract：Objective To observe the effects of berberine (BBH) pretreatment on the degree and the incubation period of epileptic seizure induced by penicillin in mice and to discuss the mechanism.Methods After adaptive feeding of 3 days,fifty male Kunming mice were randomly divided into five groups including the saline group,model group,VPA group,BBH 1 group,and BBH 2 group.The mice in the VPA group were given intraperitoneal injection of 40 mg/kg VPA,mice in the BBH 1 group were given 25 mg/kg BBH by gavage and BBH 2 group with 50 mg/kg BBH in the same way.The saline and model groups were given the same volume of saline or 25% β-cyclodextrin,and all the groups were administered once a day for three days.Up to the next day of the last time,except for the saline group,all the other four groups were given an intraperitoneal injection of 7×106 IU/kg penicillin to induce epileptic seizure.We recorded the incubation period for each group of mice from administration to the onset of epilepsy.We evaluated the onset classification byRacine criterion and recorded the seizure attack (more than III-grade).Animals showing seizure attack for 1 h were killed by dislocation of cervical vertebra.Brain tissues were taken out and processed for further estimation,we used LC-MS to test the content of glutamic acid (Glu),γ-aminobutyric acid (GABA) and serotonin (5-HT).Results As for the seizures,there were 2 cases of class Ⅲ,7 cases of class Ⅳ,1 case of class V,and 8 cases of grand mal epilepsy,respectively,in the model group;in the VPA group,they were 6,3,1,and 4;in the BBH 1 group,they were 3,6,1,and 7;in the BBH 2 group,there was i case of class II,6 cases of class Ⅲ,3 cases of class Ⅳ,1 case of class V,and 4 cases of grand mal epilepsy.The number of mice with seizures more than class Ⅲ in the BBH 2 group was significantly different as compared with that of the model group (all P<0.05).The incubation period of the model group,VPA group,BBH 1 and BBH 2 groups were (142.4±68.4),(237.5±132.6),(246.9±59.8),and (260.5±52.4)s.The incubation period of the BBH 1 and BBH 2 groups was longer than that of the model group (all P<0.05).The level of GABA in the VPA group was higher than that of the model group (P<0.05).The Glu/GABA of the model group was higher than that of the saline group (P<0.05).The Glu/GABA of the VPA group was lower than that of the model group (P<0.05).The levels of Glu/GABA in the BBH1 group and the BBH2 group were lower than that of the model group,but the difference was not statistically significant.The Glu/5-HT in the BBH1 group was lower than that of the model group (P<0.05).Conclusions The BBH pretreatment helps to reduce the scale of epileptic seizures in mice and prolong the incubation period.Among them,the overcome of 50 mg/kg dose is better than 25 mg/kg.The anti-epileptic mechanism of BBH may be associated with regulating neurotransmitter levels in the hippocampus.