基于网络药理学和分子对接法探讨乙字汤治疗痔病的作用机制

Mechanism of action of Yizi decoction in treatment of hemorrhoid based on network pharmacology and molecular docking

目的:应用网络药理学和分子对接法探究乙字汤治疗痔病的活性成分和作用机制。方法:利用Pubchem和TCMSP数据库筛选乙字汤的有效活性成分并预测作用靶点,通过Genecards数据库获取痔病相关的疾病靶点,并用UniProt数据库标准化蛋白名称。取药物疾病共同靶点,以STRING平台进行蛋白互作(PPI),借助Cytoscape3.8.0软件进行可视化分析,并构建中药-成分-靶点网络。利用Metascape数据库对交集基因进行KEGG通路分析和GO富集分析。使用Auto Dock 4对度值较高的药物成分与核心靶点进行分子对接验证,并借助Pymol和Lig Plot 2.2进行可视化分析。结果:乙字汤治疗痔病的活性成分126个,潜在靶点53个,以白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)、基质金属蛋白酶9(MMP9)、血管内皮生长因子A(VEGFA)等为核心靶点,主要通过IL-17、核因子-kappa B、丝裂原活化蛋白激酶等信号通路治疗痔病。分子对接结果显示主要活性成分与核心靶点均有较好的结合活性。结论:乙字汤的主要活性成分通过调节IL-6、TNF、MMP9、VEGFA等多种细胞因子治疗痔病。

Objective:To investigate the active components and mechanism of action of Yizi decoction in the treatment of hemorrhoid based on network pharmacology and molecular docking.Methods:Pubchem and TCMSP databases were used to screen out the effective active components of Yizi decoction and predict their action targets.Genecards database was used to obtain the disease targets associated with hemorrhoid,and UniProt database was used to standardize protein name.The common targets of the drug and the disease were obtained;STRING platform was used to establish a protein-protein interaction network,Cytoscape3.8.0 software was used for visual analysis,and a traditional Chinese medicine-component-target network was established.Metascape database was used to perform Kyoto Encyclopedia of Genes and Genomes pathway analysis and gene ontology enrichment analysis of intersecting genes.AutoDock4 was used to perform molecular docking validation of the drug components and core targets with high values,and Pymol and LigPlot 2.2 were used to perform visual analysis.Results:In the treatment of hemorrhoid,Yizi decoction had 126 active components,53 potential targets,and the core targets including interleukin-6(IL-6),tumor necrosis factor(TNF),matrix metalloproteinase-9(MMP9),and vascular endothelial growth factor A(VEGFA),and it exerted a therapeutic effect on hemorrhoid mainly through the signaling pathways such as interleukin-17,nuclear factor-kappa B,and mitogen-activated protein kinase.Molecular docking results showed good binding activity between the main active components and the core targets.Conclusion:The main active components of Yizi decoction exerts a therapeutic effect of hemorrhoid via multiple cytokines such as IL-6,TNF,MMP9,and VEGFA.