基于网络药理学探讨茜草治疗溃疡性结肠炎的作用机制

Exploring the underlying mechanism of rubia cordifolia on ulcerative colitis based on network pharmacology

目的:运用网络药理学探讨茜草治疗溃疡性结肠炎的活性成分、作用靶点及信号通路等,解释其分子作用机制。方法:应用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)筛选茜草的潜在活性成分及作用靶点。利用Cytoscape软件,通过TCMSP、GeneCards数据库构建“药物-成分-靶点-疾病”网络,并通过String平台及Cytoscape软件进行蛋白质-蛋白质相互作用(Protein-Protein Interaction,PPI)网络模型的构建,找出核心靶点。通过R语言对潜在靶点进行基因本体论(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。结果:分析结果表明,茜草中排名前3位的活性成分是β-谷甾醇、去氢-α-拉杷醌、异落叶松脂素。茜草治疗溃疡性结肠炎的潜在靶点共37个,关键靶点包括转录因子激活蛋白-1亚基JUN、半胱氨酰天冬氨酸特异性蛋白酶-3(Caspase-3,CASP3)、内皮型一氧化氮合酶(Nitric Oxide Synthase 3,NOS3)、热休克蛋白90α家族A类成员1(Heat Shock Protein HSP 90-alpha,HSP90AA1)等,主要通过影响核受体活性以及雌激素信号通路、白细胞介素17(Interleukin-17,IL-17)信号通路、糖尿病并发症晚期糖基化终末产物及其受体(AGE-RAGE)信号通路等来发挥治疗溃疡性结肠炎的作用。结论:从网络药理学的角度预测了茜草治疗溃疡性结肠炎的作用机制,证明其治疗溃疡性结肠炎具有多成分、多靶点和多途径的特点,为进一步研究提供了理论基础及方向。

Ojective:To explore the active components,target and signal pathway of rubia cordifolia on ulcerative colitis by network pharmacology,and to explain the molecular mechanism of rubia cordifolia on UC.Methods:The potential active components and the target of rubia cordifolia were screened by TCMSP.Using Cytoscape software,the network of“drug-component-target-disease”was established through TCMSP and GeneCards databases.The String platform and Cytoscape software were used to construct the PPI network and to find out the core targets.GO and KEGG enrichment analysis of potential targets was carried out by R language.Results:The results showed that the top three active components in rubia cordifolia were beta-sitosterol,xyloidone and isolariciresinol.There are 37 potential targets,and the key targets include JUN,CASP3,NOS3,HSP90AA1,etc..Rubia cordifolia plays a role on UC mainly by affecting nuclear receptor activity,estrogen signaling pathway,IL-17 signaling pathway,and AGE-RAGE signaling pathway in diabetic complications.Conclusion:This study predicted the mechanism of rubia cordifolia on UC by network pharmacology,and proved that it has the characteristics of multi-component,multi-target and multi-pathway in treating UC,which provides a theoretical basis and also a direction for further research.