基于基因表达综合数据库和网络药理学探讨香参丸治疗溃疡性结肠炎的分子机制

To explore the molecularmechanism of Xiangshenwan against ulcerative colitis based on gene expression omnibus data base and network pharmacology

目的采用生物信息学和网络药理学分析香参丸对溃疡性结肠炎(UC)的分子机制。方法2023年1―5月通过中药系统药理学数据库与分析平台(TCMSP)收集香参丸的有效成分及其相关靶点,利用基因表达综合(GEO)数据库筛选UC相关靶点,将香参丸与UC的交集靶点信息上传至STRING并通过Cytoscape 3.7.2可视化蛋白质相互作用(PPI)网络。使用Metascape数据库进行KEGG与GO通路富集分析并预测香参丸作用UC的相关通路,并绘制“中药-成分-疾病-靶点-通路”网络,利用Autodock进行分子对接。结果结果显示共筛选得到香参丸主要成分136个、靶点243个,UC相关靶点1750个,香参丸与UC交集靶点37个,筛选出关键成分槲皮素、刺芒柄花素、木犀草素以及山柰酚等,关键靶点如NOS2、PPARG、IL1B、MMP2以及ICAM1等。分子对接结果提示核心成分与核心靶点结合稳定,平均最低结合能为−5.5986 kCal/mol。KEGG与GO通路富集分析显示香参丸参与多种分子功能和生物过程,其涉及的主要通路有TNF信号通路、Toll样受体信号通路、HIF-1信号通路以及MAPK信号通路等。结论香参丸可通过多靶点、多通路改善UC症状,其主要成分槲皮素、刺芒柄花素、木犀草素以及山柰酚等可能通过TNF信号通路、Toll样受体信号通路、HIF-1信号通路以及MAPK信号通路等作用于NOS2、PPARG、IL1B、MMP2等关键靶点。

Objective To analyze the molecular mechanism of Xiangshenwan in the treatment of Ulcerative colitis(UC)by network pharmacology and bioinformatics.Methods From January to May 2023,Main components and it's targets of Xiangshenwan were ob⁃tained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the related targets of UC were obtained from GEO database.The intersection target information of Xiangshenwan and UC was uploaded to STRING and visu⁃alized by Cytoscape 3.7.2.Metascape database were used to Kyoto Encyclope dia of genes and genomes(KEGG)pathway enrichment analysis and Gene Ontology(GO)function enrichment analysis to predict the related pathways of Xiangshenwan on UC.The"drug-com⁃ponent-disease-target-access"network was plotted.Autodock was used for molecular docking prediction.Results The results of this study showed that a total of 136 components,243 targets,the 1750 UC related targets,and 37 intersection targets of Xiangshenwan and UC were screened out.The key components of Xiangshenwan were quercetin,ononetin,luteolin,and kaempferol,and key targets such as NOS2,PPARG,IL1B,MMP2 and ICAM1.The results of molecular docking showed that the core components had stable binding with the core targets,and the average minimum binding energy was−5.5986 kCal/mol.The results of KEGG pathway analysis and GO functional annotation analysis showed that Xiangshenwan were involved in a variety of molecular functions and biological processes,and the main pathways involved TNF signaling pathway,Toll-like receptor signaling pathway,HIF-1 signaling pathway,MAPK signal⁃ing pathway and so on.Conclusion Xiangshenwan exerts therapeutic effect on UC through multiply targets and multiply pathways.The main components of Xiangshenwan,such as quercetin,formononetin,luteolin and kaempferol,may act on key targets such as NOS2,PPARG,IL1B,MMP2 through TNF signaling pathway,Toll-like receptor signaling pathway,HIF-1 signaling pathway and MAPK signaling pathway.