基于网络药理学和分子对接研究人参-茯苓治疗COPD的作用机制

Mechanism of action of Panax ginseng-Poria cocos in treatment of chronic obstructive pulmonary disease: A study based on network pharmacology and molecular docking

目的:基于网络药理学和分子对接探讨人参-茯苓药对治疗慢性阻塞性肺疾病(COPD)的作用机制。方法:通过TCMSP数据库获取人参-茯苓的活性成分及靶点,在GeneCards和OMIM数据库中收集COPD的相关靶点,运用Venny 2.1获取药物-疾病的共同靶点。通过Cytoscape 3.8.2构建药物-活性成分-共同靶点-疾病及核心靶点网络图。使用R软件绘制核心靶点条形图,对共同靶点进行基因本体(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析,并采用分子对接技术对关键靶点和主要活性成分的结合能力加以验算。结果:共获得37个有效药物成分,137个映射靶点,7389个疾病靶点,61个交集靶点。初步预测人参-茯苓药对治疗COPD主要与苯代南蛇碱(Celabenzine)、阿朴天仙子碱(Aposiopola mine)、灌木远志酮A(Frutinone A)、马卡因(Iner min)等活性成分密切相关;主要包括细胞色素P4503A4酶(CYP3A4)、内皮一氧化氮合成酶(NOS3)、V-rel网状内皮细胞过多症病毒癌基因同源物A(RELA)、信号传导与转录激活因子1(STAT1)等核心靶点;GO功能富集分析提示涉及93个生物过程,KEGG通路富集分析显示涉及29条通路;分子对接结果显示对接构象合理。结论:人参-茯苓药对治疗COPD是通过多成分、多靶点、多途径协同发挥治疗作用。

Objective: To investigate the mechanism of action of Panax ginseng-Poria cocos drug combination in the treatment of chronic obstructive pulmonary disease(COPD) based on network pharmacology and molecular docking.Methods: TCMSP database was used to obtain the active components and targets of Panax ginseng-Poria cocos, GeneCards and OMIM databases were used to obtain the targets of COPD,and Venny 2.1 was used to obtain the common targets of drug and disease.Cytoscape 3.8.2 was used to construct a drug-active component-common target-disease network and a core target network.R software was used to plot the bar charts of core targets, and gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed for common targets.The molecular docking technique was used to validate the binding capacity of key targets and main active components.Results: The above analyses obtained 37 effective drug components, 137 mapped targets, 7389 disease targets, and 61 intersecting targets.Preliminary prediction showed that Panax ginseng-Poria cocos in the treatment of COPD was closely associated with the active components such as celabenzine, aposiopolamine, Frutinone A,and Maackiain.The core targets included cytochrome P4503 A4,endothelial nitric oxide synthase 3,v-rel reticuloendotheliosis viral oncogene homolog A,and signal transducer and activator of transcription 1.GO enrichment analysis showed the involvement of 93 biological processes, and KEGG pathway enrichment analysis showed the involvement of 29 pathways.The results of molecular docking showed a reasonable conformation.Conclusion: The Panax ginseng-Poria cocos drug combination exerts a synergistic therapeutic effect on COPD through multiple components, targets, and pathways.