文献类型：期刊文献

中文题名：基于网络药理学探讨甘姜苓术汤治疗纯湿型肥胖症的作用机制

英文题名：The action mechanism of the Ganjiang Lingzhu decoction on treating pure wet obesity based on network pharmacology

作者：易希善[1];康学东[2];杨维杰[2];柏婷燕[1];肖国庆[1]

第一作者：易希善

机构：[1]甘肃中医药大学,甘肃兰州730000;[2]甘肃中医药大学附属医院,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2022

卷号：14

期号：31

起止页码：11

中文期刊名：中医临床研究

外文期刊名：Clinical Journal Of Chinese Medicine

基金：甘肃省中医药管理局科研项目(GZKP-2020-30)。

语种：中文

中文关键词：甘姜苓术汤;网络药理学;分子对接;肥胖症;作用机制

外文关键词：The Ganjiang Lingzhu decoction;Network pharmacology;Molecular docking;Obesity;Action mechanism

摘要：目的:运用网络药理学方法探讨甘姜苓术汤治疗纯湿型肥胖症潜在活性成分和作用机制。方法:依靠中药系统药理学数据库与分析平台(TCMSP)筛选甘姜苓术汤(茯苓、白术、干姜、甘草)有效成分,并在TCMSP平台上预测有效成分潜在靶点,同时利用GeneCards、人类孟德尔遗传数据库(OMIM)数据库挖掘肥胖症相关靶点,将获取的活性成分靶点与疾病靶点取交集,得到甘姜苓术汤抗肥胖症的预测靶点。利用STRING平台构建预测靶点蛋白质-蛋白质相互作用网络并结合Cytoscape 3.7.0探索其蛋白质功能模块;通过Metascape数据库对预测靶点进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,并以Cytoscape软件构建“药物-化合物-疾病-基因”网络,最后采用Antudock软件及Pymol软件对甘姜苓术汤的化学成分与重要靶点进行分子对接验证。结果:甘姜苓术汤抗肥胖的核心活性成分为松苓新酸、啤酒甾醇、α-香树脂醇、12α-甲基丁酰基-14-乙酰基-8-反式白术三醇等118个,核心靶点为雌激素受体1(Estrogen Receptor 1,ESR1)、FOS原癌基因、网状内皮细胞过多症病毒癌基因同源物A(RELA)、核受体共激活因子1(Nuclear Receptor Coactivator 1,NCOA1)、周期蛋白D1(Cyclin D1,CCND1)等。GO富集分析显示与对无机物的反应、细胞对激素刺激的反应、对酮的反应、对类固醇激素的反应等生物过程相关。KEGG富集共得到140条信号通路,涉及丝裂原活化蛋白激酶(Mitogen-activated Protein Kinase,MAPK)信号通路、甲状腺激素信号通路、内分泌抵抗等。分子对接显示<-5.0 kcal/mol占总数的66.7%,验证结果显示多数成分与靶点结合活性稳定。结论:甘姜苓术汤抗纯湿型肥胖症具有多成分-多靶点-多通路的作用特点,尤其与内分泌抵抗、调节激素水平密切相关。
Objective:The potential active ingredients and action mechanism of the Ganjiang Lingzhu decoction(甘姜苓术汤)on pure wet obesity were explored through network pharmacology method.Methods:In TCMSP,the active ingredients of the Ganjiang Lingzhu decoction were screened out,and potential targets of the active ingredients were predicted in TCMSP.At the same time,obesity-related targets were mined in Gencards and OMIM databases.The obtained active ingredient targets and disease targets were intersected to obtain the predictive targets of the Ganjiang Lingzhu decoction for treating obesity.The STRING platform was used to construct a PPI network of the predicted targets,and its protein function modules were explored by Cytoscape 3.7.0.The Metascape database was used to perform the GO function and KEGG pathway enrichment analysis of the predicted targets.Cytoscape software was used to construct a“Medicine-Dompounds-Disease-Gene”network.Finally,Antudock software and Pymol software were used to verify the molecular docking between the chemical components and important targets of the Ganjiang Lingzhu decoction.Results:There were 118 core active ingredients of the Ganjiang Lingzhu decoction on obesity,including trametenolic acid,cerevisterol,α-Amyrin and so on.The core targets were ESR1,FOS,RELA,NCOA1,CCND1,etc..The GO enrichment analysis mainly involved biological processes such as the response to inorganic substances,the response of cells to hormone stimulation,the response to ketones,and the response to steroid hormones.A total of 140 signal pathways were obtained from the KEGG enrichment analysis,involving MAPK signal pathway,thyroid hormone signal pathway,endocrine resistance and so on.The molecular docking results showed that the key targets with binding energy less than-5.0 kcal/mol accounted for 66.7%of the total,and the verification results showed that most of the components had stable binding activity to the targets.Conclusion:The Ganjiang Lingzhu decoction has the characteristics of multi-component,multi-target,multi-pathway in the treatment of pure wet obesity,which is closely related to endocrine resistance and regulating hormone levels.