柴胡-钩藤配伍治疗颞叶癫痫的网络药理学和分子对接研究

Research of Chaihu-Gouteng Compatibility in Treating Temporal Lobe Epilepsy Based on Network Pharmacology and Molecular Docking

目的:基于网络药理学技术探讨柴胡-钩藤配伍治疗颞叶癫痫的作用机制,并通过分子对接技术验证柴胡-钩藤药对的有效成分与核心治疗靶点的结合情况。方法:首先,在OMIM和GeneCards数据库中检索获得颞叶癫痫相关的靶点;在TCMSP数据库中筛选柴胡-钩藤药对的有效成分及作用靶点;通过venny软件映射得到柴胡-钩藤配伍治疗颞叶癫痫的靶点。其次,使用STRING数据库对治疗靶点进行蛋白-蛋白相互作用分析;借助clusterProfiler软件包对治疗靶点进行基因本体(GO)功能富集分析、基因组百科全书(KEGG)通路富集分析,并通过Cytoscape将数据进行可视化,构建“成分-靶点-通路-疾病”多维关系网络。最后,根据分子对接技术预测有效成分与核心治疗靶点的结合情况。结果:在关系网络中,得到柴胡-钩藤配伍有效成分41种,有效成分作用于颞叶癫痫的治疗靶点共116个。治疗靶点蛋白之间具有直接或间接的相互作用关系;治疗靶点主要影响157个生物功能,涉及157个KEGG信号通路。分子对接的结果表明:柴胡-钩藤配伍的41种有效成分均与颞叶癫痫的核心治疗靶点结合良好,且大部分有效成分结合性优于丙戊酸钠、左乙拉西坦。结论:柴胡-钩藤配伍的有效成分可能通过多靶点、多通路对颞叶癫痫起治疗作用。柴胡-钩藤配伍对颞叶癫痫的疗效可能是基于其有效成分与靶点之间的结合性良好。

Objective:To explore the mechanism of Chaihu-Gouteng compatibility in the treatment of temporal lobe epilepsy based on pharmacology network,and to verify the active components of the compatibility and the core therapeutic targets by molecular docking technique.Methods:Firstly,the targets related to temporal lobe epilepsy were retrieved from OMIM and GeneCards databases;the active components and action targets of Chaihu-Gouteng compatibility were screened in the TCMSP database;Venny software mapping was used to obtain the therapeutic target of Chaihu-Gouteng compatibility in the treatment of temporal lobe epilepsy.Secondly,the STRING database was used to analyze the protein-protein interactions of the therapeutic targets;with the help of clusterProfiler software package,GO function enrichment analysis and KEGG pathway enrichment analysis were carried out on the therapeutic targets;the data were visualized by Cytoscape and construct a multi-dimensional network of‘component-target-pathway-disease’.Finally,molecular docking techniques were used to predict the binding of active components to core therapeutic targets.Results:In the relationship network,41 kinds of effective components were obtained and 116 therapeutic targets were identified for temporal lobe epilepsy.There was direct or indirect interactions between therapeutic target proteins.The therapeutic targets mainly affected 157 biological functions and involved 157 KEGG pathways.The results of molecular docking showed that the 41 active components of Chaihu-Gouteng compatibility were well combined with the core therapeutic targets of temporal lobe epilepsy,and the combination was better than Valproate and Levetiracetam.Conclusion:The active components of Chaihu-Gouteng compatibility can treat the temporal lobe epilepsy by multiple targets and multiple pathways.The efficacy of Chaihu-Gouteng compatibility on temporal lobe epilepsy may be related to the good binding between its active components and the targets.