A Preliminary Study On The Antiepileptic Effect And Mechanism Of Therapeutic Administration Of Ginsenoside Rb1

Epilepsy is a chronic neurological disorder caused by the abnormal excessive synchronous neuronal discharge in the brain.Long-term recurrent seizures have caused serious physical and psychological damage to the patient.The pathogenesis of epilepsy is complicated.At present,it is generally accepted that the imbalance of excitability and inhibition in the central nervous system is the main pathogenesis of epilepsy,and abnormal glutamate metabolism is an important reason for the imbalance between excitability and inhibition in the central nervous system.Glutamate(Glu)is the most important excitatory amino acid neurotransmitter in the central nervous system,mainly metabolized and regulated by glutamate-glutamine(Glu-Gln)cycle.Glutamate transporter and metabolic enzymes are the key components that regulate the Glu-Gln cycle and the excitability and inhibition of central nervous system.Ginsenoside Rb1 is one of the main active ingredients of ginseng.It has been shown to have various neuroprotective effects such as reducing excitotoxicity,maintaining neurotransmitter balance,reducing neuroinflammation,anti-oxidative stress and anti-apoptosis.Research had showed that preventive administration of ginsenoside Rb1 has anti-experimental epilepsy effects.However,the clinical treatment of epilepsy usually starts with drug treatment after diagnosis.Therefore,the effect of therapeutic administration of ginsenoside Rb1 on epilepsy and the mechanism of action need to be further explored.In this study,pentylenetetrazole(PTZ)was used to establish an epilepsy model.After the model was successfully established,ginsenoside Rb1 was given to intervene to explore the anti-epileptic effect of its therapeutic administration,and explore its mechanism of action based on the key transporter and enzyme of the Glu-Gln cycle.This experiment is divided into two parts,and the research contents of each part are described as follows:Part ?:Efficacy and protection of ginsenoside Rbl therapeutic administration on epileptic miceObjective:To explore the effect of ginsenoside Rbl therapeutic administration on the general state,seizure symptoms and brain neuron damage in PTZ induced epileptic mice.Methods:The epilepsy model was established by intraperitoneal injection of subconvulsant dose of pentylenetetrazole(PTZ).The mice were randomly divided into PTZ group,VPA group and low-dose(10 mg·kg-1),mid-dose(20 mg·kg-1)and high-dose(40 mg·kg-1)ginsenoside Rbl groups.Each group was intraperitoneally injected with corresponding medicine for 30 days,once a day.The severity of seizures and the recovery of therapeutic administration in mice were evaluated by observing the general state,seizure stage and seizure latency at different time points after administration;the degeneration of neurons in hippocampal CA1 of mice was observed by FJB staining.Results:Compared with the control group,the mice in the PTZ group were lethargic,their activities were reduced,the seizure stage increased(P<0.01),the seizure latency decreased(P<0.01),and the number of FJB positive cells in hippocampal CA1 area increased significantly(P<0.01).After 30 days therapeutic administration,compared with the PTZ group,the mental state improved,their activities increased,the seizure stage significantly decreased(P<0.01),the seizure latency significantly increased(P<0.05),and the number of FJB positive cells in hippocampal CA1 area significantly decreased(P<0.05)in VPA group and low-dose,middose and high-dose ginsenoside Rb1 groups.Conclusion:Therapeutic administration of ginsenoside Rb1 can effectively improve the mental state and activity status of epileptic mice,relieve the severity of seizures,and reduce nerve cell damage.Part ?:Effect of ginsenoside Rbl on the key links of Glu-Gln cycle in the cortex and hippocampus of epileptic miceObjective:To explore the effect of ginsenoside Rbl on the key transporter and enzyme of the Glu-Gln cycle in the cortex and hippocampus of epileptic mice,and to preliminarily explore its anti-epileptic mechanism.Methods:The Glu content and GS activity in cortex and hippocampus were detected by biochemical method;the mRNA expression of GLT-1 and GS in cortex and hippocampus were detected by RT-PCR;the protein expression of GLT-1 and GS in cortex and hippocampus were detected by Western Blot.Results:Compared to the control group,the Glu content significantly increased(P<0.01)and GS activity,GLT-1 and GS mRNA and protein expression significantly decreased(P<0.01)in cortex and hippocampus of mice in the PTZ group.After 30 days therapeutic administration,compared to the PTZ group,the Glu content decreased and GS activity,GLT-1 and GS mRNA and protein expression increased in cortex and hippocampus of mice in VPA group and lowdose,mid-dose and high-dose ginsenoside Rb1 groups.Among them,the mid-dose and highdose of ginsenoside Rbl and VPA had more significant effects(P<0.05).Conclusion:Ginsenoside Rb1 may regulate Glu metabolism by up-regulating the key links of Glu-Gln cycle GLT-1 and GS expression and activity,thereby exerting anti-epileptic effects and improving nerve cell damage.In conclusion,this study used the PTZ igniting method to establish an epilepsy mouse model.After the model was successfully established,ginsenoside Rbl was given to intervene.It was found that the therapeutic administration of ginsenoside Rbl can relieve the severity of epileptic seizures and improve brain tissue nerve cells injury,has anti-epileptic effects,and its mechanism of action may be related to up-regulating the key links of Glu-Gln cycle GLT-1 and GS expression and activity,thereby regulating Glu metabolism.