基于网络药理学和分子对接技术探讨清肺解毒汤治疗肺纤维化的作用机制

Exploration of the Mechanism of Qingfei Jiedu Decoction in the Treatment of Pulmonary Fibrosis Based on Network Pharmacology and Molecular Docking Technology

目的:采用网络药理学和分子对接技术挖掘清肺解毒汤(QFJDT)治疗肺纤维化(PF)的作用机制。方法:通过TCMSP数据库,获取QFJDT的配方活性成分,利用Swiss Target Prediction数据平台对靶标进行预测。使用GeneCards数据库收集PF相关的靶标,并与药物作用靶标相比较,筛选出共同部分,作为药物成分作用的预测靶标。进而使用Cytoscape3.6.1绘制“药物-成分-基因-疾病”网络图、构建蛋白互作网络(PPI),并筛选出核心靶标。最后对潜在作用靶点进行GO功能富集分析和KEGG通路富集分析,建立成分-靶点-通路网络,并对关键靶点进行核心化合物分子对接。结果:从TCMSP中获取QFJDT有效活性成分280个,靶点4571个;从GeneCards数据库获取PF相关基因5149个;通过构建“药物-成分-基因-疾病”网络获得QFJDT治疗PF的关键靶点224个;通过GO富集分析发现QFJDT治疗PF与3340个生物过程有关,包括抗氧化反应、对活性氧的反应等。KEGG富集涉及164条信号通路,表明QFJDT主要通过糖尿病并发症中的AGEs-RAGE信号通路等发挥治疗PF的作用,最后以花生四烯酸5-脂氧合酶靶蛋白与QFJDT中15个主要活性成分进行分子对接,发现橘皮素、香豆酚C、山奈酚等多个成分均表现出较好的亲和力,表明其与PF已知靶标有直接作用关系。结论:QFJDT包含多个与PF有抑制作用的药效成分,可通过多成分多靶标协同起效的作用机制发挥药效,本文可进一步为研究QFJDT治疗PF的药效物质基础及作用靶点提供参考。

Objective:To explore the mechanism of Qingfei Jiedu Tang(QFJDT)in treating pulmonary fibrosis(PF)by using network pharmacology and molecular docking technology.Methods:The TCMSP database was used to obtain the active ingredients of the QFJDT formulation and the targets were predicted using the Swiss Target Prediction data platform.GeneCards database was used to collect targets related to pulmonary fibrosis and compare them with the drug action targets to screen out common parts as predicted targets for drug ingredient action.Then,Cytoscape 3.6.1 was used to draw the"drug-component-genes-disease"network diagram,construct the protein-protein interaction(PPI)network,and screen out the core targets.Finally,GO functional enrichment and KEGG pathway enrichment analyses were carried out for the potential targets,and the component-targetpathway network was established,and molecular docking of core compounds was carried out for the key targets.Results:A total of 280 active ingredients and 4571 targets of QFJDT were obtained from TCMSP;and 5149 PF-related genes were obtained from GeneCards database;A total of 224 key targets of QFJDT for PF were obtained by constructing a"drug-ingredient-genes-disease"network.The GO enrichment analysis revealed that the treatment of pulmonary fibrosis by QFJDT was related to 3340 biological processes,including antioxidant response and response to reactive oxygen species.KEGG enrichment involved 164 signaling pathways,indicating that QFJDT played a role in the treatment of PF mainly through the AGEs-RAGE signaling pathway in diabetic complications,etc.Finally,molecular docking of arachidonic acid 5-lipoxygenase target proteins with the 15 major active ingredients in QFJDT revealed that several components,such as cellulose,coumarin C,and kaempferol,showed good affinity,suggesting that they had a direct action relationship with the known targets of PF.Conclusion:QFJDT contains a number of pharmacodynamic components with inhibitory eff ects on PF,which can exert pharmacodynamic eff ects through the synergistic mechanism of multi-component and multi-target action.This paper can further provide a reference for the study of the pharmacodynamic material basis and target of action of QFJDT for the treatment of PF.