GEO数据挖掘结合网络药理学及分子对接技术探究托里消毒散治疗克罗恩病的潜在机制

GEO data mining combined with network pharmacology and molecular docking techniques to explore the potential mechanism of Tuoli Xiaodu Powder for the treatment of Crohn’s disease

目的通过生物信息学数据挖掘方法寻找克罗恩病相关基因,使用网络药理学方法及分子对接技术研究托里消毒散治疗克罗恩病的作用靶点与潜在的作用机制。方法克罗恩病的相关基因从基因表达综合数据库(GEO database)、孟德尔遗传数据库(OMIM)与人类遗传数据库(Gene card)获取,在TCMSP数据库与UniProt数据库确定托里消毒散组方成分的活性化合物和对应靶点,并通过Cytoscape软件实现疾病-复方调控网络构建,对疾病与托里消毒散复方交叉基因进行PPI网图构建并确定核心基因靶点,进行基因本体论(GO)生物功能分析和基因组的京都百科全书(KEGG)通路富集分析来阐明发挥作用的生物功能与分子通路,对核心化合物成分与核心靶点使用分子对接技术验证其结合能力。结果克罗恩病相关基因合并去重后共得到922个,中药复方相关活性化合物241个,经Durgbank校对得到123个复方相关基因,疾病-复方交叉基因共23个,网络药理学选取出的核心化合物是槲皮素、木犀草素、非瑟酮、山柰酚、甘草查尔酮A,PPI网图确定的核心基因靶点是ALB、IL6、ESR1、PPARG、VEGFA、EGFR。交叉基因的GO分析提示基因富集在DNA结合转录因子活性的调节、脂质储存的调节等方面,KEGG通路富集在多个癌症、TNF、NF-κB通路等;分子对接验证显示化合物配体与蛋白受体的结合能力良好。结论托里消毒散组方成分可能通过相关受体蛋白作用于多种癌症、TNF、NF-κB通路,来调节炎症、免疫机制控制克罗恩病的发展。

Objective We searched for Crohn’s disease(CD)related genes through bioinformatics data mining,and used network pharmacology methods and molecular docking techniques to investigate the targets and potential mechanisms of action of Tuoli Xiaodu Powder(Vital Qi Strengthening and Toxin Removing Powder)for the treatment of CD.Methods The genes related to CD were obtained from the GEO database,Online Mendelian Inheritance in Man(OMIM)and GeneCards,and the active compounds and corresponding targets of the components of the Tuoli Xiaodu Powder were identified in the TCMSP database and the UniProtdatabase,and the disease-formula regulatory network was created with Cytoscapes.The PPI network was constructed for the crossover genes between the disease and the prescription and the core gene targets were identified.Results A total of 922 CD related genes were obtained after deduplicating,241 active compounds related to Chinese herbal compound,123 compoundrelated genes were obtained by Durgbank proofreading of the corresponding targets,and a total of 23 disease-formula crossover genes were selected by network pharmacology,and the core compounds selected by network pharmacology were quercetin,luteolin,fisetin,kaempferol,and licochalconeA.The core gene targets identified by PPI network map were ALB,IL6,ESR1,PPARG,VEGFA,and EGFR.The GO analysis of the crossover genes suggested that the genes were enriched in the regulation of DNA-binding transcription factor activity,regulation of lipid storage,etc.,and the KEGG pathway was enriched in multiple cancer,TNF,and NF-κB pathways;molecular docking validation showed good binding ability of compound ligands to protein receptors.Conclusion The ingredients of Tuoli Xiaodu Powder may act on a variety of cancer,TNF,and NF-κB pathways through related receptor proteins to regulate inflammatory,immune mechanisms to control the development of CD.