基于网络药理学和分子对接探讨蒙药额尔敦-乌日勒治疗癫痫的潜在作用机制

Exploring the Potential Mechanism of Mongolian Medicine Erdun-Uzil in the Treatment of Epilepsy Based on Network Pharmacology and Molecular Docking

利用网络药理学筛选额尔敦-乌日勒抗癫痫的作用靶点及潜在作用机制,为临床治疗癫痫提供理论依据。从有关文献中确定额尔敦-乌日勒的有效成分,采用TCMSP数据库筛选出额尔敦-乌日勒的有效活性成分及靶标;通过TTD、OMIM数据库筛选癫痫的预测靶点,将两者靶点进行映射交集,利用STRING数据库构建蛋白互作网络图并筛选出47个核心靶点;再通过AmiGO2平台进行GO(Gene Ontology)生物过程和KEGG信号通路富集分析,利用Cytoscape 3.7.2软件构建活性成分-关键靶点-通路网络图,分子对接显示木犀草素、3-甲基环十五烷酮对MAOA、MMP9、EGFR等具有较强的亲和力。网络药理学研究提示,额尔敦-乌日勒通过降低表皮生长因子(EGF)的mRNA表达,促进癫痫凋亡因子表达和增强脑内抑制性神经递质的表达,通过多途径抑制脑内神经元的同步化放电,从而达到治疗癫痫的目的。通过探讨蒙药额尔敦-乌日勒治疗癫痫多靶点多通路的作用特点,为额尔敦-乌日勒治疗癫痫的下一步研究及临床应用提供理论依据。

Through network pharmacology,screening Erdun-Uzil antiepileptic target and potential mechanism of action,to provide theoretical basis for clinical treatment of epilepsy.The effective components of Erdun-Uzil were determined from relevant literatures,and the effective active components and targets of Erdun-Uzil were screened by TCMSP database.Predictive targets of epilepsy were screened through TTD and OMIM databases,and the two targets were mapped and interacted.A protein interaction network map was constructed using the STRING database,and 47 core targets were screened out.Then,GO(Gene Ontology)biological processes and KEGG signaling pathway enrichment analysis were performed on AmiGO2 platform.Cytoscape 3.7.2 software was used to construct the active componentkey targets-pathway network diagram.The molecular docking showed that luteolin and 3-methylcyclopentadecanone had strong affinity for MAOA,MMP9 and EGFR.The network pharmacological studies suggest that Erdun-Uzil can treat epilepsy by reducing the expression of Epidermal Growth Factor(EGF)mRNA,promoting the expression of epileptic apoptosis Factor and enhancing the expression of inhibitory neurotransmitters in the brain,and inhibiting the synchrotron of neurons in the brain through multiple ways.The function characteristics of multi-target multi-pathway of Mongolian medicine Erdun-Uzil in the treatment of epilepsy were preliminarily demonstrated,which provided theoretical basis for further research and clinical application of Erdun-Uzil in the treatment of epilepsy.