桂枝-柴胡治疗慢性心衰伴抑郁的网络药理学研究

Clinical effect of Ramulus Cinnamomi-Bupleurum chinense in treatment of chronic heart failure with depression: An analysis based on network pharmacology

目的:运用网络药理学方法挖掘桂枝-柴胡治疗慢性心力衰竭(CHF)伴抑郁(MDD)的主要活性成分、靶点及信号通路,探究其潜在作用机制。方法:通过TCMSP数据库和相关文献检索桂枝-柴胡主要活性成分及其作用靶点,经BATMAN-TCM平台对预测靶点予以补充,构建药物靶点库;通过GeneCards、DisGeNET数据库分别获取CHF与抑郁相关靶标,二者取交集,建立疾病靶标库;利用R语言将药物靶点库与疾病靶标库取交集,构建Venn图;通过STRING数据库和Cytoscape 3.7.1软件及其内在插件构建化合物-靶标网络及PPI核心网络;最后利用DAVID数据库对核心网络靶点进行GO富集和KEGG通路注释分析。结果:筛选出桂枝-柴胡有27个活性成分,288个靶基因;筛选出CHF伴MDD相关靶基因882个,药物与疾病Venn图提取关键靶点83个,PPI核心网络构建筛选出12个关键基因;GO分析(P<0.05且靶点基因富集度>10%)得到19条生物过程,13条细胞组分表达过程,8个分子功能相关过程;KEGG分析(P<0.05)显示72条信号通路,包括HIF-1信号通路、TNF信号通路、PI3K-Akt信号通路、神经活性配体-受体相互作用信号通路等。结论:桂枝-柴胡活性成分通过多成分、多靶点、多通路发挥CHF伴MDD的治疗作用。

Objective: To investigate the main active components, targets, and signaling pathways of Ramulus Cinnamomi-Bupleurum chinense in the treatment of chronic heart failure(CHF) with major depressive disorder(MDD) and its potential mechanism of action based on network pharmacology.Methods: TCMSP database and related articles were searched to obtain the main active components of Ramulus Cinnamomi-Bupleurum chinense and their targets, and the BATMAN-TCM platform was used to supplement predictive targets and establish a drug target database.GeneCardsand DisGeNET databases were used to obtain the targets associated with CHF and depression, respectively, and an intersection was determined to establish a disease target database.R language was used to obtain the intersection of the drug target database and the disease target database and construct the Venn diagram.STRINGdatabase and Cytoscape 3.7.1 software with its plug-ins were used to construct a component-target network and a protein-protein interaction(PPI) core network.Finally, DAVID database was used to perform the gene ontology(GO) enrichment analysis and KEGG pathway annotation analysis of core network targets.Results: A total of 27 active components and 288 target genes of Ramulus Cinnamomi-Bupleurum chinense were screened out.A total of 882 target genes associated with CHF with MDD were screened out;83 key targets were obtained by the Venn diagram of the drug target database and the disease target database, and 12 key genes were screened out by the PPI core network.GO analysis(P<0.05 and target gene enrichment >10%) obtained 19 biological processes, 13 cellular component expression processes, and 8 molecular function-related processes, and KEGG analysis(P<0.05) obtained 72 signaling pathways, including the HIF-1 signaling pathway, the TNF signaling pathway, the PI3 K-Akt signaling pathway, and theneuroactive ligand-receptor interaction signaling pathway.Conclusion: The active components of Ramulus Cinnamomi-Bupleurum chinense exerta therapeutic effect on CHF with MDD via multiple components, targets, and pathways.