基于网络药理学研究孔圣枕中丹“异病同治”失眠及健忘的作用机制

Mechanistic analysis of Sagacious Confucius'Pillow Elixir in the treatment of insomnia and amnesia with concept of "treating different diseases with same method" based on network pharmacology

关键词:  网络药理学  孔圣枕中丹  失眠  健忘  异病同治

Key words:  network pharmacology  Sagacious Confucius'Pillow Elixir  insomnia  amnesia  treating different diseases with same method

摘要:

[目的] 基于网络药理学方法研究孔圣枕中丹“异病同治”失眠及健忘的潜在作用机制。[方法] 利用检索中药系统药理学数据库与数据分析网络平台（TCMSP）和中药主要成分靶点网络平台HIT 2.0、中医药整合药理学研究平台（TCMIP）及中国天然产物化学库等网络平台，筛选孔圣枕中丹组方药物的活性成分，经蛋白质数据库（Uniprot）提取其活性成分的作用靶点，再结合比较毒理基因组学数据库（CTD）数据库提取与失眠和健忘有关的作用靶点。将药物活性成分作用的靶点和疾病治疗靶点比对筛选后，利用Cytoscape 3.7.1软件构建了SCPE治疗失眠与健忘的“药物-成分-靶点-疾病”网络模型。利用蛋白质相互作用数据库（String）绘制了蛋白相互作用（PPI）网络，以寻找关键靶点。利用注释、可视化和综合发现数据库（DAVID）、基因注释与分析数据库（Metascape）、R语言（R studio）软件等平台开展的生物过程数据分析，得出了热图（Heatmap）分析、基因本体（GO）富集分析和京都基因与基因组百科全书（KEGG）富集分析结果。[结果] 获得了符合条件的孔圣枕中丹活性成分39个，失眠、健忘相关靶点分别为24 771、55 876个，孔圣枕中丹“异病同治”失眠及健忘的共有靶点83个，生物过程富集分析取前20条孔圣枕中丹治疗失眠和健忘的信号通路包括肿瘤坏死因子（TNF）信号通路、血管内皮生长因子（VEGF）信号通路、p53信号通路、cGMP-PKG信号通路等，表明孔圣枕中丹“异病同治”失眠及健忘的主要机制可能涉及抗细胞凋亡、炎症反应、神经递质调节、泛素蛋白连接酶结合等。[结论] 孔圣枕中丹“异病同治”失眠及健忘涉及多成分、多靶点以及多通路，可为阐释中药复方“异病同治”科学内涵提出了全新的思路与方式，也为孔圣枕中丹进一步的机制研究和新的临床运用带来了生物信息学理论依据。

Abstract:

[Objective] To explore the possible mechanism of Sagacious Confucius'Pillow Elixir in the treatment of insomnia and amnesia with concept of "treating different diseases with same method" by the network pharmacology.[Methods] Using TCMSP,HIT 2.0,TCMIP,natural Product Chemistry Database of China and other network platforms,to screen the active ingredients of Sagacious Confucius'Pillow Elixir (SCPE) formula.The targets of its active ingredients were extracted from Uniprot protein database (Uniprot),and the targets related to insomnia and amnesia were extracted from the Comparative Toxicological Genomics Database (CTD).After comparing and screening the targets of drug active components and disease targets,Cytoscape 3.7.1 software was used to construct a "drug-component-target-disease" network model for SCPE treatment of insomnia and amnesia.Protein interaction (PPI) networks were mapped using the Protein Interaction Database (String) to find key targets.Biological process data analysis using annotation,Visualization and Integrated Discovery Database (DAVID),Gene Annotation and Analysis Database (Metascape),R Studio software and other platforms,the results of Heatmap analysis,Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were obtained.[Results] We obtained 39 active components of SCPE,24 771 targets for insomnia and 55 876 targets for amnesia,83 targets of SCPE for insomnia and amnesia.Biological process enrichment analysis of the top 20 signal pathway of SCPE for insomnia and amnesia include tumor necrosis factor (TNF) signal pathway,vascular endothelial growth factor (VEGF) signal pathway,p53 signal pathway,CPMP-PKG signal pathway,etc.The main mechanisms of insomnia and amnesia of SCPE may involve anti-apoptosis,inflammatory response,neurotransmitter regulation,ubiquitin protein ligase binding,etc.[Conclusion] Insomnia and amnesia involve multiple components,multiple targets and multiple pathways,which provides a new idea and way to explain the scientific connotation of TCM compound "treating different diseases with the same treatment" and also provide bioinformatics theoretical basis for further mechanism research and new clinical application of SCPE.