乌梅丸治疗溃疡性结肠炎的网络药理学研究

Network pharmacology study of Wumei Pill in the treatment of ulcerative colitis

目的:运用网络药理学方法分析乌梅丸治疗溃疡性结肠炎(UC)的潜在作用机制,为进一步实验研究提供理论参考。方法:检索TCMSP、TTD、Drugbank、pharmGKB、Uniprot、DisGeNET数据库,筛选乌梅丸化学成分作用靶点及UC相关的靶点,采用Cytoscape软件构建乌梅丸化学成分-靶点-疾病网络,通过Clue GO对靶点相关的基因功能和信号通路进行分析,预测乌梅丸治疗UC的潜在靶点。结果:从乌梅丸中共筛选出508个化学成分,对应的6178个靶点中与UC相关的有26个,其中PTGS2、NOS3、NOS2、TNF、Bcl-2、MMP9、IL-6、IL-10、IL-2、ICMA1等10个靶点可能为乌梅丸治疗UC的重要靶点;乌梅丸可能影响与UC相关的Fc-RI、胞质DNA、HIF-1、Toll-样受体、TNF、T细胞受体、Jak-STAT、NF-κB、IL-17等多个信号通路,调控免疫炎症反应、细胞增殖和凋亡、活性氧代谢、趋化因子生物合成、内皮屏障建立、血管内皮生长因子产生,对病毒防御反应、干扰素产生、异型细胞与细胞粘附正调控,寄主共生体生长负调控等多个生物过程,从而发挥干预UC的作用。芝麻素、槲皮素、小檗碱、醋酸、棕榈酸、人参皂苷等可能是乌梅丸治疗UC的主要药效物质基础。结论:乌梅丸治疗UC的作用机制可能与其多成分作用于多靶点,影响与UC相关的多个信号通路,调节复杂的生物过程有关。

Objective:To Study on the potential mechanism of Wumei pill in treating ulcerative colitis based on network pharmacology,and provide theoretical basis for further research.Methods:Database of TCMSP,TTD,Drugbank,PharmGKB,Uniprot,DisGeNET were screened for Wumei pill chemical component targets and UC related targets.Cytoscape software was used to establish chemical components-targets-disease network of Wumei pill.The gene function and signal pathway of the target were analyzed by Clue GO to predict the potential target of Wumei Pill for the treatment of UC.Results:508 chemical components were screened from Wumei pill,26 targets were found related to UC among 6178 targets.Ten of the targets including PTGS2,NOS3,NOS2,TNF BCL2,MMP9,IL6,IL10,IL2,and ICMA1 were suggested important targets for Wumei pill treating UC.Wumei pill may affect many signal pathways related to UC,such as Fc-RI,cytoplasmic DNA,HIF-1,Toll-like receptor,TNF,T-cell receptor,Jak-STAT,NF-kappa B and IL-17.It also regulates multiple biological processes such as the immune inflammatory response,cell proliferation and apoptosis,reactive oxygen species metabolism,chemokine biosynthesis,establishment of endothelial barrier,Vascular endothelial growth factor production,viral defense response,interferon production,positive regulation of cell adhesion and negative regulation of host symbiosis growth.It is found that Sesamin,quercetin,berberine,acetic acid,palmitic acid and ginsenoside may be the main effective substances of Wumei Pill in treating UC.Conclusion:The mechanism of Wumei Pill in treating UC is related to its multi-components acting on multiple targets,regulating complex biological processes by affecting multiple signal pathways related to UC.