基于网络药理学和分子对接初探自拟化浊解毒方治疗溃疡性结肠炎作用机制

Mechanism of Huazhuo Jiedu Decoction in the Treatment of Ulcerative Colitis Based on Network Pharmacology and Molecular Docking

目的:基于网络药理学和分子对接探讨自拟化浊解毒方治疗溃疡性结肠炎的作用机制。方法:通过中药系统药理学数据库(TCMSP),筛选自拟化浊解毒方的药物活性成分及对应的靶点。使用GeneCards数据库、DisGeNET数据库筛选收集溃疡性结肠炎的疾病相关靶点。运用韦恩图对药物活性成分靶点和疾病靶点取交集,利用Cytoscape软件绘制“活性成分-靶点”网络,根据计算度值(Degree),筛选主要活性化合物。使用String数据库对活性成分-靶点交集靶点进行PPI网络构建。利用R语言对交集靶点进行GO和KEGG富集分析。使用AutoDock Vina软件将药物活性成分与核心靶点分子对接。结果:自拟化浊解毒方11味药物中有7个共有成分,257个靶点基因,获得溃疡性结肠炎相关靶点2 941个,得到交集基因170个。槲皮素、异鼠李素、木犀草素、山柰酚、β-谷甾醇等为其主要活性成分,PPI网络图显示调控的核心靶点包括AKT1、TP53、TNF、IL6等。GO富集分析获得742个条目。KEGG富集分析通路有180条。分子对接显示药物主要活性成分与核心靶点结合能均<-6 kcal/mol,结合稳定。结论:自拟化浊解毒方治疗溃疡性结肠炎,通过多成分、多靶点、多途径实现,为后续实验研究和临床验证提供了思路。

Objective:This study is to explore the mechanism of self-designed Huazhuo Jiedu decoction(HZJD) in the treatment of UC based on network pharmacology and molecular docking.Methods:Firstly, the components and the corresponding targets of HZJD were screened based on the TCMSP platform.The disease targets associated with UC were collected by GeneCards database and DisGeNET database.The intersection of drug active ingredient targets and disease targets were obtained by venn diagram.Then, the “active component-target”network was drawn by Cytoscape software, and the main active compounds were screened by Network Analyzer according to the degree of calculation.The intersection targets were imported into String database to construct PPI network.GO functional enrichment analysis and KEGG pathways enrichment analysis were performed on the intersected targets through R language.Lastly molecular docking was used to evaluate the binding activity of the active components to the key targets.Results:Showed that a total of 7 active ingredients and 257 target genes were screened in the 11 drugs of self-designed HZJD.2 941 targets related to ulcerative colitis and a total of 170 intersection genes were obtained.Quercetin, Isorhamnetin, luteolin, kaempferol, β-sitosterol are the main active components of HZJD.The results of PPI network diagram showed that AKT1,TP53,TNF,IL6,IL1B,etc.,were the core targets.GO analysis obtain 742 items.KEGG enrichment analysis revealed 180 pathways.The binding energies of the main active ingredients and the core targets were all less than-6kcal/mol, and the binding was stable.Conclusion:The research we have done suggests that the treatment of ulcerative colitis by self-designed HZJD is realized by multi-component, multi-target and multi-approach, which provides ideas for further experimental research and clinical verification.