基于网络药理学探讨葛根芩连汤治疗溃疡性结肠炎潜在作用机制

Potential Mechanism of Gegen Qinlian Decoction in Treatment of Ulcerative Colitis Based on Network Pharmacology

目的:运用网络药理学技术筛选葛根芩连汤治疗溃疡性结肠炎(ulcerative colitis,UC)的主要活性成分,预测活性成分的作用靶点,建立单味药-活性成分-作用靶点网络,进一步探讨葛根芩连汤治疗溃疡性结肠炎的潜在效应机制。方法:利用中药系统药理学技术平台(traditional chinese medicine systems pharmacology database and analysis platform,TCMSP)收集葛根芩连汤中4味中药的化学成分,借助人类基因数据库(GeneCards)获取UC的相关靶点基因,将药物作用靶点和疾病相关靶标基因取交集得到该方治疗UC的关键作用靶点,使用String数据库对关键作用靶点构建蛋白质相互作用网络,并通过Cytoscape软件将结果可视化。借助DAVID和ClueGo对关键作用靶点进行基因本体(gene ontology,GO)分析和基因组百科全书(KEGG)通路富集。结果:共收集葛根芩连汤138个活性成分和27个关键作用靶点。其中,STAT3、TNF、CXCL8、IL1B、VEGFA、TP53、IL10、AKT1等关键基因主要通过调控NF-κB、IL-17、Toll样受体、MAPK、PI3K-Akt、Jak/STAT、TNF等信号通路,在细胞外泌体、质膜外侧、细胞核中发挥作用。结论:葛根芩连汤治疗溃疡性结肠炎是多靶点、多个信号通路共同调节的复杂过程,预测葛根芩连汤治疗溃疡性结肠炎的潜在机制,为深入研究葛根芩连汤治疗溃疡性结肠炎的作用机制提供理论依据与参考。

Objective:To screen the main active ingredients of Gegen Qinlian Tang for the treatment of ulcerative colitis(UC)by using network pharmacology technology,to predict the target of active ingredients and to establish a single drug-Active ingredient-target network,to further explore the potential effect mechanism of Gegen Qinlian Decoction on ulcerative colitis.Methods:The traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was used to collect the chemical constituents of the four flavors of traditional Chinese medicine in Gegen Qinlian Tang,and the relevant target genes of UC were obtained with the help of the Human Gene Database(GeneCards)to apply the drugs.The target and disease-related target genes are taken to obtain the key role of the treatment of UC.The String database is used to construct a protein interaction network for the key role and the results are visualized by Cytoscape software.With the help of DAVID and ClueGo,gene ontology(GO)analysis and KEGG pathway enrichment were performed on key target targets.Results:A total of 138 active ingredients and 27 key targets of Gegen Qinlian Decoction were collected.Among them,STAT3,TNF,CXCL8,IL1B,VEGFA,TP53,IL10,AKT1 and other key genes mainly through the regulation of NF-κB,IL-17,Toll-like receptors,MAPK,PI3K-Akt,Jak/STAT,TNF and other signaling pathways,and play roles in cell exosomes,outside the plasma membrane,and the nucleus.Conclusion:Gegen Qinlian Decoction is a complex process with multiple targets and multiple signal pathways.It predicts the potential mechanism of Gegen Qinlian Decoction in treating ulcerative colitis.The mechanism of action of sexual colitis provides theoretical basis and reference.