痛泻要方异病同治溃疡性结肠炎与肠易激综合征的网络药理学及分子对接研究

Mechanism of action of Tongxieyaofang homotherapy for heteropathy in treatment of ulcerative colitis and irritable bowel syndrome:A study based on network pharmacology and molecular docking

目的:利用网络药理学与分子对接方法探究痛泻要方异病同治溃疡性结肠炎(UC)和肠易激综合征(IBS)的潜在机制。方法:利用TCMSP数据库结合文献检索筛选痛泻要方活性成分,通过PubChem和SwissTargetPrediction数据库预测药物靶点,分别从GeneCards、DisGeNET、OMIM数据库获取UC和IBS疾病靶点,运用微生信Venn绘图工具得到疾病与药物交集靶点,运用Cytoscape软件绘制网络图;利用STRING构建蛋白质-蛋白质相互作用(PPI)网络并筛选核心靶点;在BioGPS中检索核心靶点在器官组织的分布信息;对交集靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析,并通过分子对接验证核心靶点和主要活性成分的结合活性。结果:痛泻要方中β-谷甾醇、山柰酚、柚皮素等活性成分通过作用于SRC激酶、丝裂原活化蛋白激酶3(MAPK3)、磷脂酰肌醇-3激酶调节亚基1(PIK3R1)、丝裂原活化蛋白激酶1(MAPK1)等核心靶点来干预体内炎症调节、巨细胞病毒及EB病毒感染、氧化应激、细胞自噬/凋亡等途径而发挥作用。核心靶点主要分布在伯基特淋巴瘤、平滑肌、结肠等部位。分子对接显示主要活性成分与核心靶点之间具有良好的结合活性。结论:痛泻要方通过多成分、多靶点、多通路抑制肠道炎症,调节免疫失衡,改善结肠组织氧化应激,并从抗病毒,改善肠道菌群,修复肠黏膜屏障等途径发挥异病同治UC和IBS的作用。

Objective:To investigate the mechanism of action of Tongxieyaofang homotherapy for heteropathy in the treatment of ulcerative colitis(UC) and irritable bowel syndrome(IBS) based on network pharmacology and molecular docking.Methods:TCMSP database and literature were searched to obtain the active components of Tongxieyaofang,PubChem and SwissTargetPrediction databases were used to predict disease targets,and GeneCards,DisGeNET,and OMIM databases were used to obtain the disease targets of UC and IBS.The Venn tool on Weishengxin website was used to obtain the intersecting targets of disease targets and drug targets,and Cytoscape was used to construct a network;STRING was used to construct a protein-protein interaction(PPI) network and screen for core targets;BioGPS was used to obtain the information on the distribution of core targets in organs and tissue;the gene ontology functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed for the intersecting targets,and molecular docking was performed to investigate the binding activity between core targets and main active components.Results:By acting on the core targets including SRC,MAPK3,PIK3R1,and MAPK1,the active components(including beta-sitosterol,kaempferol,and naringenin) in Tongxieyaofang exerted a therapeutic effect by intervening in the pathways such as inflammatory regulation,cytomegalovirus/EB virus infection,oxidative stress,and cell autophagy/apoptosis.The core targets were mainly distributed in Burkitt lymphoma,smooth muscle,and the colon.Molecular docking showed good binding activity between the main active components and the core targets.Conclusion:Tongxieyaofang can inhibit intestinal inflammation,regulate immune imbalance,and improve oxidative stress in colon tissue via multiple components,targets,and pathways,and it exerts a role of homotherapy for heteropathy in the treatment of UC and IBS by intervening against virus infection,improving intestinal flora,and repairing intestinal mucosal barrier.