基于数据挖掘和网络药理学探讨中药治疗失眠障碍伴抑郁、焦虑的分子机制

Molecular Mechanism of Traditional Chinese Medicine in the Treatment of Insomnia Disorder with Depression and Anxiety Based on Data Mining and Network Pharmacology

目的基于数据挖掘和网络药理学方法探讨中药治疗失眠障碍伴抑郁、焦虑的核心组方及作用机制。方法使用古今医案云平台V2.2.3将中国知网、万方、维普数据库中近5年中药治疗失眠障碍伴抑郁、焦虑的处方进行药物频次、属性统计及关联、聚类和复杂网络分析,获得用药规律及核心组方。运用中药系统药理学数据库与分析平台(TCMSP)、GeneCards等数据库分析核心组方,分别得到相关成分靶点和疾病靶点并取交集,利用Cytoscape V3.6.0和STRING数据库分别构建网络,并在Metascape数据库和ClueGO插件中进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,最终选取关键成分和关键靶点应用AutoDock Vina进行分子对接。结果数据挖掘共得到方剂189首,涉及中药212味;通过药物关联、聚类和复杂网络分析综合得到核心组方为柴胡、白芍、酸枣仁、茯苓、甘草。共获得核心组方有效成分91种,靶点217个,交集基因66个,核心成分包括花生酸、脱氢表皮酸等,核心靶点包括肿瘤坏死因子、血管内皮生长因子A等。GO功能富集分析包括血液循环、神经递质水平调节等;KEGG通路富集分析包括神经活性配体-受体相互作用、血清素能突触等;关键成分和关键靶点分子对接结果显示其均可形成稳定结合。结论初步得到中药治疗失眠障碍伴抑郁、焦虑的用药规律及核心组方多成分、多靶点、多通路作用机制。

Objective To explore the core formulations of traditional Chinese medicine in the treatment of insomnia disorder with depression and anxiety and its mechanism based on data mining and network pharmacology.Methods Using the ancient and modern medical record cloud platform V2.2.3 drug frequency,attribute statistics and correlation,clustering and complex network analysis of the prescriptions of traditional Chinese medicine for insomnia disorder with depression and anxiety were performed to obtain the medication rules and core prescriptions.The core prescriptions were obtained by Traditional Chinese Medicine System Pharmacology Database,and Analysis Platform(TCMSP),GeneCards,and other databases were used to obtain the relevant active ingredient targets and disease targets respectively.Cytoscape V3.6.0 and STRING databases were used to construct networks respectively,and Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed in Metascape database and ClueGO plugin.Key effective components and key targets were selected and docking AutoDock Vina.Results A total of 189 prescriptions were obtained through data mining,involving 212 traditional Chinese medicine.Through drug association,clustering and complex network analysis,it was concluded that the core formulas were bupleurum,radix paeoniae alba,suanzaoren,poria,and licorice.A total of 91 active ingredients,217 targets,and 66 intersection genes were obtained.The core ingredients include arachidonic acid,dehydro epidermic acid,and the core targets include tumor necrosis factor and vascular endothelial growth factor A.The results of GO functional enrichment analysis included blood circulation,neurotransmitter level regulation.The results of KEGG pathway enrichment analysis included neuroactive ligand-receptor interactions,serotonergic synapses.Molecular docking of key components and key targets molecules showed that stable binding could be formed.Conclusion The result of prescription regularity of traditional Chinese medicine in the treatment of insomnia disorder with depression and anxiety showed tranditional Chinese medicine treats multi-component,multi-target,and multi-pathway mechanism.