治疗心力衰竭中药有效成分网络药理学研究

Network Pharmacology Study of the Effective components of Traditional Chinese Medicine in the Treatment of Heart Failure

目的:应用网络药理学技术探讨用于治疗心力衰竭中药方剂的活性成分及作用机制。方法:通过方剂现代应用数据库收集心力衰竭防治相关的中药复方,并从中选取出现频次较高的单味药,使用CNPC和TCMSP数据库收集化学成分。从TCMSP、CTD等数据库获得活性成分靶点。利用TTD、GeneCardes和DisGeNET等数据库搜集疾病靶点。采用STRING数据库和Cytoscape 3.2.1软件构造PPI网络分析。运用ClueGO插件进行KEGG信号通路分析和DAVID数据库进行基因功能富集分析。结果:检索得到治疗心力衰竭的53种中药方剂、76个活性成分、594个化合物靶点及430个疾病靶点。网络分析结果表明,筛选出的五种中药可能通过缺氧应答、炎症、细胞凋亡等过程,酶结合、蛋白结合、血红素结合等分子功能发挥作用。其作用机制可能与AGERAGE信号通路、HIF-1信号通路、IL-17信号通路、FoxO信号通路、TNF信号通路及PI3K-Akt信号通路等多种信号通路有关。结论:本文针对治疗HF的中药方剂,通过数据挖掘,分析了丹参、葶苈子、黄芪和桂枝等中药的有效成分抗心衰作用靶点及通路,并构建了蛋白质相互作用网络、化学成分-靶点网络、靶点-通路网络,初步揭示了中药复方抗HF的物质基础及多种有效成分的协同作用机制,为后续相关研究提供基础。

Objective:To explore the active ingredients and mechanism of traditional Chinese medicine prescriptions for treating heart failure(HF)by network pharmacology.Methods:Chinese herbal prescriptions and monomers for the treatment of HF were collected through the modern application database of prescriptions and several single herbs with the top use frequency were chosen for further study.The chemical constituents of these herbs were collected from databases CNPC and TCMSP.Active ingredient targets were obtained from TCMSP,CTD and other databases.TTD,GeneCardes and DisGeNET databases were used to collect disease targets.PPI network analysis was constructed using STRING database and Cytoscape 3.2.1 software.The ClueGO was used to analyze KEGG pathway enrichment and DAVID database for GO functional enrichment analysis.Results:53 traditional Chinese medicine prescriptions,76 active components,594 compound targets,and 430 disease targets were retrieved.The results of network analysis showed that the five selected Chinese medicines may play its anti-heart failure role by regulating hypoxia,inflammation,apoptosis,enzyme binding,protein binding,heme binding and other molecular functions.The mechanism may be related to AGE-RAGE signaling pathway,HIF-1 signaling pathway,IL-17 signaling pathway,FoxO signaling pathway,TNF signaling pathway and PI3K-Akt signaling pathway.Conclusion:This paper is aimed at the traditional Chinese medicine prescriptions for HF treatment,through data mining,analyzed the effective components,targets and pathways of Danshen,Tinglizi,Huangqi and Guizhi,and constructed the protein interaction network,the component-target network and the target-pathway network,preliminarily revealed the material basis of traditional Chinese medicine prescriptions against HF and the synergistic mechanism of various active components,providing a basis for subsequent relevant studies.