基于生物信息学探讨败酱散调控氧化应激缓解克罗恩病的机制

Mechanism of Baijiang San in alleviating Crohn's disease by regulating oxidative stress based on bioinformatics analysis

  • 摘要:
    目的 采用生物信息学分析探讨败酱散通过调节氧化应激(OS)缓解克罗恩病(CD)的作用靶点及潜在机制。
    方法 利用TCMSP数据库获取败酱散的活性成分及其所对应的靶标。在GEO数据库中下载CD相关数据集(GSE36807、GSE59071、GSE102133), 将差异分析得到的CD差异基因作为疾病治疗靶标。在Genecards数据库中搜索OS相关基因, 并获取药物活性成分与疾病、OS相关基因的共同作用靶点。使用Cytoscape软件构建“化合物-靶点”调控网络; 在String数据库制作蛋白互作(PPI)网络,将数据导入Cytoscape软件使用Cytohubba插件筛选核心靶点;利用R软件进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析; 使用Mirtarbase数据库、Starbase数据库、Targetscan数据库预测微小RNA(miRNA); 使用Enrichr数据库预测转录因子(TF), 使用Cytoscape软件构建“miRNA-TF-mRNA”调控网络。
    结果 CD差异基因175个,其中上调基因135个、下调基因40个。TCMSP数据库中败酱散有效成分: 薏苡仁9个,附子21个,败酱草13个。使用Cytohubba筛选排名前5的核心基因是白细胞介素-1β(IL-1β)、前列腺素内过氧化物合成酶2(PTGS2)、CXC趋化因子配体8(CXCL8)、细胞间黏附分子-1(ICAM1)、血管内皮细胞生长因子受体(KDR), 药物成分对应靶点较多的是槲皮素、山奈酚; KEGG富集分析的主要通路是糖尿病并发症中的晚期糖基化终产物及其受体(AGE-RAGE)信号通路、核因子κB(NF-κB)信号通路、肿瘤坏死因子(TNF)信号通路等;数据库中预测到76个miRNA, 5个转录因子。
    结论 败酱散通过调控OS缓解CD的机制是多成分、多靶点、多通路的生物过程。

     

    Abstract:
    Objective To explore the target and potential mechanism of Baijiang San in alleviating Crohn's disease (CD) by regulating oxidative stress (OS) based on bioinformatics analysis.
    Methods The active ingredients of Baijiang San and their corresponding targets were obtained by using TCMSP database. CD related datasets (GSE36807, GSE59071 and GSE102133) were downloaded from GEO database, and the CD differential genes obtained by differential analysis were used as targets for disease treatment. CD differential genes obtained by differential analysis were used as therapeutic targets for diseases. OS-related genes were searched in Genecards database, and the common targets of drug active ingredients, diseases and OS-related genes were obtained. Cytoscape software was used to construct the "compound-target" regulatory network; the protein-protein interaction (PPI) network was made in String database, and the data were imported into Cytoscape software to screen the core targets using Cytohubba plug-in; R software was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis; microRNA (miRNA) was predicted by Mirtarbase database, Starbase database and Targetscan database; the Enrichr database was used to predict transcription factor (TF) and Cytoscape software was used to construct "miRNA-TF-mRNA" networks.
    Results There were 175 differential CD genes, including 135 up-regulated genes and 40 down-regulated genes. In TCMSP database, Baijiang San included 9 effective ingredients in Yiyiren, 21 effective ingredients in Fuzi and 13 effective ingredients in Baijiangcao. The top 5 core genes screened by Cytohubba were interleukin-1β (IL-1β), prostaglandin-endoperoxide synthase 2 (PTGS2), C-X-C motif chemokine ligand 8 (CXCL8), intercellular adhesion molecule 1 (ICAM1), vascular endothelial cell growth factor-A receptor (KDR). Quercetin and kaempferol were the most common targets of drug components. The main pathways of KEGG enrichment analysis were advanced glycation end product (AGE)-receptor for AGE (AGE-RAGE) signaling pathway, nuclear factor-kappa B (NF-κB) signaling pathway and tumor necrosis factor (TNF) signaling pathway in diabetic complications; a total of 76 miRNAs and 5 transcription factors were predicted.
    Conclusion The mechanisms of Baijiang San in alleviating CD by regulating OS are a multi-component, multi-target and multi-pathway biological process.

     

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