基于网络药理学的黄芪桂枝五物汤治疗胃溃疡功效研究与初步验证  

Efficacy Study and Preliminary Verification of Huangqi Guizhi Wuwu Decoction(黄芪桂枝五物汤)in Treating Gastric Ulcer Based on Network Pharmacology

作　　者：陈婷[1] 王伟[2] 刘维菊[3] 曹志群[1] 王云鹏[2] 姜璐[2] 薛晔[1] 胡冬青[2] 李玲玲[1] CHEN Ting;WANG Wei;LIU Weiju;CAO Zhiqun;WANG Yunpeng;JIANG Lu;XUE Ye;HU Dongqing;LI Lingling(Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Shandong Hospital of Traditional Chinese Medicine,Jinan 250011,China;Qianfoshan Hospital of Shandong Province,Jinan 250014,China)

机构地区：[1]山东中医药大学,山东济南250355 [2]山东省中医院,山东济南250011 [3]山东省千佛山医院,山东济南250014

出　　处：《山东中医药大学学报》2021年第2期199-208,共10页Journal of Shandong University of Traditional Chinese Medicine

基　　金：国家自然科学基金青年项目(编号:81704038,81904128);山东省中医经典名方协同创新中心项目(编号:2019KFY15);山东省博士后创新计划项目(编号:202003069)。

摘　　要：目的:通过网络药理学方法系统化探究黄芪桂枝五物汤治疗胃溃疡的功效网络,并用分子对接技术进行验证。方法:利用中药系统药理学数据库与分析平台(TCMSP)获取黄芪桂枝五物汤的有效化合物及作用靶点,利用在线人类孟德尔遗传数据库(OMIM)、基因疾病关联数据库(DisGeNET)、人类基因数据库(GeneCards)、毒性与基因比较数据库(CTD)获取胃溃疡的疾病靶点,经靶点映射获取黄芪桂枝五物汤与胃溃疡的共同作用靶点,通过STRING数据库获取靶点之间的关系信息,应用Cytoscape 3.6.2可视化处理,并通过生物学信息注释数据库(DAVID)进行基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析。运用Schrodinger软件包完成分子对接。结果:共获得槲皮素、β-谷甾醇、蛇床子素、ent-表儿茶素等58个有效化学成分和抑癌基因p53(TP53)、前列腺素内过氧化物合酶(PTGS2)、血管内皮生长因子A(VEGFA)、肿瘤坏死因子(TNF)、丝裂原活化蛋白激酶1(MAPK1)、白细胞介素-6(IL-6)等35个作用靶点,经GO富集分析得到生物学过程261个,细胞组分29个,分子功能37个,经KEGG富集分析得到79条相关通路,其中与PI3K/Akt信号通路、TNF信号通路、缺氧诱导因子-1(HIF-1)信号通路密切相关。分子对接示靶蛋白与主要化学成分结合能较强,结合力好。结论:黄芪桂枝五物汤以多成分、多靶点、多通路的特点实现抗胃溃疡作用,为后期实验验证提供依据。Objective:To systematically explore the efficacy network of Huangqi Guizhi Wuwu Decoction(黄芪桂枝五物汤)in the treatment of gastric ulcer by means of network pharmacology and verify it with molecular docking.Methods:Traditional Chinese medicine system pharmacology database and analysis platfor(TCMSP)was used to obtain the effective compounds and targets of Huangqi Guizhi Wuwu Decoction,Online Mendelian Inheritance in Man(OMIM),Database of Gene-Disease associations(DisGeNET),Human Gene Database(GeneCards),Comparative Toxicogenomics Database(CTD)database were used to obtain the disease targets of gastric ulcer,target mapping was used to obtain the common targets of Huangqi Guizhi Wuwu Decoction and gastric ulcer,and the data of the interaction between the targets was obtained through STRING database,and Cycloscape 3.6.2 was used for visualization.The gene ontology(GO)analysis and the Kyoto gene and genome encyclopedia(KEGG)pathway enrichment analysis were carried out through the DAVID database.Molecular docking was completed by Schrodinger software package.Results:A total of 58 active chemical components,including quercetin,β-sitosterol,osthol,ent-epicatechin,etc.and 35 effect target,including tumor suppressor gene p53(TP53),prostaglandin-endoperoxide synthase 2(PTGS2),vascular endothelial growth factor A(VEGFA),tumor necrosis factor(TNF),mitogen activated protein kinase 1(MAPK1),interleukin-6(IL-6),etc.were obtained.Total 261 biological processes,29 cell components and 37 molecular functions were obtained by GO enrichment analysis.Total 79 related pathways were obtained by KEGG enrichment analysis,which were closely related to PI3K/Akt signal pathway,TNF signal pathway and hypoxia inducible factor-1(HIF-1)signal pathway.Molecular docking indicated that the binding energy of target protein and main chemical components was strong and the binding force was good.Conclusion:Huangqi Guizhi Wuwu Decoction can achieve the therapeutic effect of gastric ulcer through multi-component,multi-target and multi-channel,w

关 键 词：黄芪桂枝五物汤 胃溃疡 有效成分 靶点 分子对接技术 网络药理学 

分 类 号：R2-03[医药卫生—中医学]