基于网络药理学和分子对接探讨疏风止痉方治疗耐药性癫痫的作用机制

Study on the mechanism of Shufeng Zhijing Prescription in the treatment of drug-resistant epilepsy based on network pharmacology and molecular docking

关键词:  网络药理学  疏风止痉方  耐药性癫痫  作用机制  分子对接

Key words:  network pharmacology  Shufeng Zhijing Prescription  drug-resistant epilepsy  action mechanism  molecular docking

摘要:

[目的] 探讨疏风止痉方治疗耐药性癫痫的作用机制。[方法] 在中药系统药理数据库（TCMSP）筛选疏风止痉方12味中药活性成分，并预测作用靶点；运用GeneCards、OMIM数据库获取耐药性癫痫相关基因，获得DRE相关靶点；利用R4.0.0语言筛选药物和疾病的交集靶点，借助String数据库构建靶点蛋白互作网络；通过Cytoscape 3.7.2软件构建中药-化学成分-疾病靶点网络；使用R语言进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析，利用Cytoscape软件构建KEGG关系网络；最后通过AutoDock Vina对重要化合物作分子对接验证。[结果] 得到潜在作用靶点165个，筛选出槲皮素、木犀草素、山柰酚、汉黄芩素、柚皮素5个主要化学成分，7个核心靶点PT－GS2、HSP90AA1、ESR1、AR、MAPK1、AKT1、MAPK3，基因富集分析得到2 584条GO功能条目和171条KEGG通路。分子对接结果表明疏风止痉方中主要活性成分与核心作用靶点具有良好的结合活性。[结论] 该研究初步揭示了疏风止痉方治疗耐药性癫痫的作用机制，主要是通过抗病毒、抑制炎症、神经保护等作用起到协同增效作用，为临床合理应用提供了理论依据。

Abstract:

[Objective] To explore the mechanism of Shufeng Zhijing Prescription in the treatment of drug-resistant epilepsy.[Methods] The 12 active components of Shufeng Zhijing Prescription were screened from the pharmacological database (TCMSP) of traditional Chinese medicine system,and the action targets were predicted;drug-resistant epilepsy-related genes were obtained by GeneCards and OMIM databases,and DRE-related targets were obtained.The intersection targets of drugs and diseases were screened by R4.0.0 language,and the target protein interaction network was constructed with the help of String database.The traditional Chinese medicine-chemical composition-disease target network was constructed by Cytoscape3.7.2 software;the enrichment analysis of GO and KEGG was carried out by R language,and the KEGG relationship network was constructed by Cytoscape software.Finally,the molecular docking of important compounds was verified by AutoDockVina.[Results] Finally,165 potential targets and quercetin,luteolin,kaempferol,wogonin and naringin were screened out.2 584 GO functional items and 171 KEGG pathways were identified by gene enrichment analysis of 7 core targets:PTGS2,HSP90AA1,ESR1,AR,MAPK1,AKT1 and MAPK3.The results of molecular docking showed that the main active components of Shufeng Zhijing Prescription had good binding activity to the core targets.[Conclusion] This study reveals the mechanism of Shufeng Zhijing Prescription in the treatment of drug-resistant epilepsy,which mainly plays a synergistic effect through antiviral,anti-inflammation and neuroprotection,which provides a theoretical basis for rational clinical application.