畜牧与兽医2024，Vol.56Issue(6)：78-85,8.
基于数据库挖掘、网络药理学和试验验证探究葡萄籽多酚缓解溃疡性结肠炎的作用机制
The mechanism of grape seed polyphenols in alleviating ulcerative colitis based on database mining,network pharmacology and experimental validation
摘要
Abstract
The aim of this study was to investigate the mechanisms by which grape seed polyphenols alleviate ulcerative colitis induced by dextran sulfate sodium.Two datasets from the GEO database were selected and integrated using the sva package.Weighted gene co-expres-sion network analysis was employed to identify gene modules associated with ulcerative colitis.Gene functions were annotated using gene on-tology databases and the kyoto encyclopedia of genes and genomes database.Then,the main components of grape seed polyphenols were de-tected using liquid chromatography-mass spectrometry.The top 10 components were selected,and their target genes were predicted using da-tabases such as TCMSP,DrugBank,and Swiss Target Prediction.The intersection of the target genes of grape seed polyphenols and the iden-tified ulcerative colitis-related modules was determined.Protein-protein interaction network analysis was performed to identify key targets of grape seed polyphenols in alleviating ulcerative colitis.Next,molecular docking was employed to validate the binding activity between the main components of grape seed polyphenols and key targets.Finally,the effects of grape seed polyphenols on the expression of the key target genes were validated using fluorescence quantitative PCR in Raw264.7 cells.The results showed that three modules were highly correlated with the phenotype of ulcerative colitis,with genes being mainly associated with inflammatory responses,cell cycle and metabolism,and cell chemotaxis.The main components of grape seed polyphenols included catechin,epicatechin,procyanidin B2,and procyanidin C1,among others.Fifteen target genes overlapped between these components and the genes in the ulcerative colitis-related modules.Among these,cy-clooxygenase-2(PTGS2),matrix metalloproteinase 9(MMP9),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)exhibited the highest connectivity in the network and were considered key targets.The top 10 components of grape seed polyphenols showed good bind-ing activity with these four targets,as confirmed by fluorescence quantitative PCR,which demonstrated the ability of grape seed polyphenols to influence the expression of these key target genes.In conclusion,grape seed polyphenols are most likely to alleviate ulcerative colitis by af-fecting PTGS2,MMP9,IL-6,and TNF-α.关键词
溃疡性结肠炎/网络药理学/分子对接/加权基因共表达网络/葡萄籽多酚/作用机制Key words
ulcerative colitis/network pharmacology/molecular docking/weighted gene co-expression network analysis/grape seed poly-phenols/mechanism分类
农业科技引用本文复制引用
王政,宋祖晨,余蕊宏,周彦彤,马岩,刘振广..基于数据库挖掘、网络药理学和试验验证探究葡萄籽多酚缓解溃疡性结肠炎的作用机制[J].畜牧与兽医,2024,56(6):78-85,8.基金项目
国家自然科学基金项目(32273048) （32273048）
