基于网络药理学与分子对接的连夏消痞颗粒治疗功能性消化不良机制分析  

Mechanism analysis of functional dyspepsia treated by Lianxiaxiaopi Granules based on network pharmacology and molecular docking

作　　者：孙彩虹 李瑞明[2,3] 田野 黄爱岚 刘杨 何毅 Sun Caihong;Li Ruiming;Tian Ye;Huang Ailan;Liu Yang;He Yi(School of Traditional Chinese Medicine,China Pharmaceutical University,Nanjing 211198;Development Center of Modern Chinese Medicine,Research Institute of Tasly Holding Group Co Ltd,Tianjin 300410;State Key Laboratory of Critical Technology in Innovative Chinese Medicine,Tasly Pharmaceutical Group Co Ltd,Tianjin 300410;Development Center of Chemicals,Research Institute of Tasly Holding Group Co Ltd,Tianjin 300410)

机构地区：[1]中国药科大学中药学院,江苏211198 [2]天士力控股集团有限公司研究院现代中药开发中心,天津300410 [3]天士力医药集团股份有限公司创新中药关键技术国家重点实验室,天津300410 [4]天士力控股集团有限公司研究院化学药品开发中心,天津300410

出　　处：《天津药学》2021年第1期19-25,共7页Tianjin Pharmacy

基　　金：国家科技重大专项“中医药优势领域的创新中药关键技术开发研究”(No.2017ZX09301005)。

摘　　要：目的:本研究采用网络药理学与分子对接探讨连夏消痞颗粒治疗功能性消化不良的潜在作用机制。方法:基于连夏消痞颗粒全方物质基础研究,采用TCMSP等数据库搜集活性化合物及其作用靶点,OMIM、DrugBank等数据库搜集FD的靶点并结合文献对疾病靶点进行整理筛选。采用STRING数据库进行蛋白质-蛋白质相互作用(PPI)网络构建并筛选出核心靶点;利用Cytoscape软件构建化合物-靶点-通路网络;随后对核心靶点进行基因本体(Gene Oncology,GO)功能富集分析及KEGG通路富集分析。最后,基于DOCK 6.0对核心靶点和活性小分子进行分子对接验证。结果:本研究共筛选出活性化合物27个,度值较高的活性化合物为β-谷甾醇、汉黄芩素、柚皮素、黄芩素、木蝴蝶素A、木兰花碱、小檗碱、巴马汀等;核心靶点10个,分别是AKT1、IL6、MAPK3、VEGFA、FOS、TNF、CASP3、TP53、JUN、PTGS2。通过GO富集分析得到条目106条,靶点富集到的信号通路167条。分子对接结果进一步验证小檗碱、黄芩素可能通过作用于核心靶点调节TNF信号通路、IL-17信号通路及Toll样受体信号通路等通路来发挥治疗作用。结论:本研究通过活性化合物-靶点-通路相互作用网络以及分子对接技术探讨连夏消痞颗粒对FD的潜在作用机制,为后续深入研究其药理作用提供了参考依据。Objective:To explore the potential mechanism of the main active ingredients of Lianxiaxiaopi Granules(LXXP)in the treatment of functional dyspepsia(FD)by using network pharmacology and molecular docking.Methods:On the basis of the pre-functional chemical identification,the databases of TCMSP,etc.,were used to collect active compounds and their targets.Databases,such as OMIM and DrugBank,were used to collect FD targets,and literature was used to organize and screen disease targets.Based on the STRING platform,protein-protein interaction(PPI)networks were constructed and then screened out core targets.Cytoscape software was used to build a compound-target-pathway network.Gene Oncology(GO)functional enrichment analysis and KEGG pathway enrichment analysis were then performed on core targets.Finally,molecular docking verification of core targets and active small molecules was performed based on DOCK 6.0.Results:A total of 27 active compounds were screened out in this study.The active compounds with high degree values were beta-sitosterol,wogonin,naringenin,baicalein,oroxylin A,magnoflorine,berberine,palmatine.The 10 core targets of action were AKT1,IL6,MAPK3,VEGFA,FOS,TNF,CASP3,TP53,JUN,PTGS2.130 entries were obtained by GO enrichment analysis,and 167 signal pathways were enriched by the targets.The molecular docking results further validated that berberine and baicalein may exert a therapeutic role by acting on core targets regulating TNF signaling pathway,IL-17 signaling pathway,and Toll-like receptor signaling pathway.Conclusion:This study investigates the potential mechanism of LXXP on FD through the active compound-target-pathway interaction network and molecular docking techniques and provides a reference basis for further study of its pharmacological effects.

关 键 词：功能性消化不良 连夏消痞颗粒 网络药理学 分子对接 作用机制 

分 类 号：R975[医药卫生—药品]