首页|基于网络药理学和生物信息学探讨薏苡附子败酱散调节铁死亡治疗溃疡性结肠炎的作用

基于网络药理学和生物信息学探讨薏苡附子败酱散调节铁死亡治疗溃疡性结肠炎的作用

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本研究旨在运用生物信息学方法探讨薏苡附子败酱散(Yiyi Fuzi Baijiangsan,YYFZBJS)调节铁死亡治疗溃疡性结肠炎(ulcerative colitis,UC)的潜在分子机制.运用网络药理学方法获取薏苡附子败酱散的成分与作用靶点,随后获取其与UC疾病基因和铁死亡相关基因的交集,通过GSE206285 数据集提取出"YYFZBJS-UC-铁死亡"差异基因的表达情况,并进行相关性分析、KEGG与GO分析.使用LASSO与SVM机器学习两种方法,进一步筛选关键差异基因,对其进行基因集富集分析(gene set enrichment analysis,GSEA)和基因集变异分析(gene set variation analysis,GSVA),以评价这些基因在不同表达时作用途径的差别.将关键基因进行免疫浸润分析以及相关性分析,建立ceRNA调控图,探究lncRNA-miRNA-mRNA之间的联系,并通过GSE87473 验证集验证上述基因的准确性,使用Cytoscape 3.9.1 软件进行degree排序;使用分子对接进一步验证相关靶点的可靠性.共获得 27 个"YYFZBJS-UC-铁死亡"差异基因,筛选发现关键基因与M0 巨噬细胞、M2 巨噬细胞、中性粒细胞等具有密切联系;验证集发现其中BRD2、HIF-1A、IDH1、PPARG、PPARA仍然具有显著性差异,degree排序得到前三的基因HIF-1A、PPARG、NQO1,分子对接结果显示YYFZBJS有效成分豆甾醇、苯甲酰乌头原碱、异红草苷与 HIF-1A、PPARG具有稳定的结合效应.综上,本研究发现薏苡附子败酱散调节铁死亡治疗 UC 的机制可能是通过调控 HIF-1A、PPARG等基因发挥药效作用,本研究为UC的治疗提供了新的参考.
Exploring the Potential Mechanisms of Yiyi Fuzi Baijiangsan on Regulating the Ferroptosis of Ulcerative Colitis via Network Pharmacology and Bioinformatics
The purpose of this study was to explore the potential molecular mechanism of YYFZBJS(Yiyi Fuzi Baijiangsan)in regula-ting ferroptosis in the treatment of ulcerative colitis(UC)by bioinformatics method.The components and action targets of YYFZBJS were obtained by the method of network pharmacology,and then intersected with UC disease genes and ferroptosis related genes.The differential gene expression of"YYFZBJS-UC-ferroptosis"was extracted by GSE206285 data set,and the correlation analysis,KEGG and GO analysis were carried out.LASSO and SVM machine learning methods were used to further screen the key differential genes and analyze them by gene set enrichment analysis(GSEA)and gene set variation analysis(GSVA)to evaluate the differences in the ac-tion pathways of these genes in different expression.Secondly,the key genes were analyzed by immune infiltration analysis and correla-tion analysis,the ceRNA regulation map was established,the relationship between lncRNA-miRNA-mRNA was explored,and the ac-curacy of the above genes was verified by GSE87473 verification set,and degree sequencing was carried out by Cytoscape 3.9.1 soft-ware.Finally,molecular docking was used to further verify the reliability of related targets.A total of 27"YYFZBJS-UC-ferroptosis"differential genes were obtained.It was found that the key genes were closely related to M0 macrophages,M2 macrophages,neutrophils and so on.The verification set found that there were still significant differences in BRD2,HIF-1A,IDH1,PPARG and PPARA.The first three genes HIF-1A,PPARG and NQO1 were obtained by degree sequencing.The results of molecular docking showed that stig-masterol,benzoylaconitine and isoorientin had stable binding effect with HIF-1A and PPARG.To sum up,this study found that the mechanism of YYFZBJS regulating ferroptosis treatment of UC may be through the regulation of HIF-1A,PPARG and other genes to play a role in drug effect,which provides a new reference for the treatment of UC.

Yiyi Fuzi BaijiangsanUlcerative colitisFerroptosisBioinformaticsNetwork pharmacologyMolecular docking

李倪仁、曾译萱、邓丙英、鲁思凡、古玉凤、朱晨、陈磊、刘怡

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南方医科大学中医药学院,广东省中药制剂重点实验室,广东省中西医结合防治情志病基础研究卓越中心,广州,510515

广州中医药大学第二附属医院药学部,广州,510120

广东药科大学中药学院,广州,510006

薏苡附子败酱散 溃疡性结肠炎 铁死亡 生物信息学 网络药理学 分子对接

国家自然科学基金项目国家自然科学基金项目广东省自然科学基金项目广州市科技基础与应用基础项目

82073982818729802023A1515011060202201011445

2024

基因组学与应用生物学
广西大学

基因组学与应用生物学

CSTPCD北大核心
影响因子:1.108
ISSN:1674-568X
年,卷(期):2024.43(8)