基于网络药理与分子对接探讨资生汤治疗COPD潜在分子机制

Investigation on the potential molecular mechanism of Zisheng Decoction in the treatment of COPD based on network pharmacology and molecular docking

目的借助网络药理学与分子对接方法探讨资生汤治疗慢性阻塞性肺疾病(COPD)的分子机制。方法利用中药系统药理学数据库与分析平台(TCMSP)获得资生汤中4味主要中药的相关化学成分和药物作用靶点;运用GeneCards数据库获取COPD疾病靶点,并将疾病靶点与药物靶点取交集作为药物作用的潜在靶点,再用David数据库进行基因本体(GO)和京都基因和基因组百科全书(KEGG)分析。然后采用STRING数据库协同Cytoscape软件生成“药物-有效成分-靶点”网络图及潜在作用靶点蛋白质相互作用(PPI)网络,根据拓扑学参数筛选资生汤治疗COPD的关键活性成分及其相对应的作用靶点。最后运用分子对接技术验证活性成分与作用靶点之间的结合能力。结果本文共筛选出资生汤活性成分8个和作用靶点78个,涉及COPD潜在作用靶点17个。利用Cytoscape软件进行拓扑分析得到白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)、白细胞介素-1β(IL-1β)等9个关键靶点。GO分析得到88个条目,KEGG分析得到8条通路,主要涉及Toll样受体(TLR)关键信号通路。分子对接结果提示8种有效成分与IL-6、IL-1β、TNF 3种核心靶点均具有较好的结合性。结论资生汤可能是通过抑制TLR信号通路,下调IL-6、IL-1β、TNF等炎症因子水平来达到治疗COPD的效果。

Objective To investigate the molecular mechanism of Zisheng Decoction in the treatment of chronic obstructive pulmonary disease(COPD)by means of network pharmacology and molecular docking.Methods The relevant chemical ingredients and drug action targets of 4 main Chinese materia medica in Zisheng decoction were obtained by using traditional chinese medicine systems pharmacology database and analysis platform(TCMSP).The GeneCards database was used to obtain COPD disease targets,and the intersection of disease targets and drug targets was taken as the potential targets of drug action.Then David database was used for gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)analysis.Then,the"drug-active ingredient-target"network diagram and the potential target protein interaction(PPI)network were generated by using the STRING database in cooperation with Cytoscape software.According to the topological parameters,the key active ingredients of Zisheng Decoction in the treatment of COPD and their corresponding action targets were screened.Finally,molecular docking technology was used to verify the binding ability between active ingredients and action targets.Results In this paper,a total of 8 active ingredients and 78 action targets of Zisheng decoction were screened,involving 17 potential action targets of COPD.A total of 9 key targets,including interleukin-6(IL-6),tumor necrosis factor(TNF)and interleukin-1β(IL-1β),etc.,were obtained by topological analysis with Cytoscape software.GO analysis resulted in 88 entries,and KEGG analysis resulted in 8 pathways,mainly involving the key signaling pathway of Toll-like receptor(TLR).The results of molecular docking indicated that the 8 effective ingredients had better binding with 3 core targets,namely IL-6,IL-1βand TNF.Conclusion Zisheng Decoction may achieve the effect of treating COPD by inhibiting TLR signalingpathway and down-regulating the levels of inflammatory factors such as IL-6,IL-1βand TNF.