Research on the Antiepileptic Mechanism of Herb Pairs Polygala Tenuifolia and Gastrodia Elata Based on the GABA-AT/GAT-1 Signaling Pathway
Objective To investigate the effects of herb pairs Polygala tenuifolia and Gastrodia elata on the latency,spatial memory,emotional response,ABAT/GAT1/GAD 65/GABRA1 protein expression levels,neuronal protection,and explore the possible mechanism of this drug in treating epilepsy in epileptic mice.Methods The successfully modeled mice were randomly divided into a model group(n=6),a high-dose(YTH,300 mg·kg-1,n=6),a medium dose(YTM,100 mg·kg-1,n=6),a low-dose(YTL,30 mg·kg-1,n=6)group of herb pairs Polygala tenuifolia and Gastrodia elata,and a control group.The effects of herb pairs Polygala tenuifolia and Gastrodia elata on spatial memory impairment and emotional response in PTZ induced chronic epilepsy mouse models were investigated using open field and elevated cross detection.HE staining was used to observe hippocampal lesions in mouse brain tissue,and protein immunoblotting was used to detect ABAT/GAT1/GAD 65/GABRA1 protein expression levels in mouse hippocampus.Immunofluorescence was used to detect the number of immune positive cells in mouse brain tissue.Molecular simulation docking analysis was performed to investigate the interaction between internal standard components of herb pairs Polygala tenuifolia and Gastrodia elata and potential targets.Results Compared with the model group,herb pairs Polygala tenuifolia and Gastrodia elata significantly prolonged the latency of epileptic seizures in mice,improved spatial memory impairment and emotional response induced by pentylenetetrazole(PTZ)in chronic epileptic mice,regulated the level of GABA-AT/GAT-1 molecular signaling pathway,downregulated the increased expression of GAD 65,GABRA1,GABA-AT,and GAT-1 in the hippocampus caused by epileptic seizures(P＜0.05),and reduced hippocampal neuronal loss.Its internal standard components can bind well to GABA-AT and GABAA receptors(GABAAR).Conclusion Herb pairs Polygala tenuifolia and Gastrodia elata can treat epilepsy through the GABA-AT/GAT-1 pathway,improve spatial memory and emotional response damage in epilepsy model mice,and protect neurons.
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