基于网络药理学-分子对接探析灭幽汤“异病同治”慢性萎缩性胃炎和胃溃疡的作用机制  

Exploring the mechanism of Mie-you decoction“homotherapy for heteropathy”to chronic atrophic gastritis and gastric ulcer using network pharmacologymolecular docking

作　　者：王思宇 周淑伟 喻斌[1] Siyu Wang;Shuwei Zhou;Bin Yu(Department of Gastroenterology,The First Hospital of Hunan University of Chinese Medicine,Changsha 410007,Hunan,China;Department of Radiology,Jiangsu Key Laboratory of Molecular and Functional Imaging,Zhongda Hospital,Medical School,Southeast University,Nanjing 210009,Jiangsu,China)

机构地区：[1]湖南中医药大学第一附属医院,湖南长沙410007 [2]东南大学附属中大医院,江苏南京210009

出　　处：《Journal of Chinese Pharmaceutical Sciences》2024年第3期258-271,共14页中国药学（英文版）

基　　金：Hunan Provincial Department of Education Scientific Research Project (Grant No.20A371);Key Project of Hunan Administration of Traditional Chinese Medicine (Grant No.C2022016);Research Program Project of Hunan University of Traditional Chinese Medicine (Grant No.zyydx201727);Clinical Technology Innovation Project of Hunan Provincial Department of Science and Technology (Grant No.2021SK51403)。

摘　　要：本研究旨在运用网络药理学分析方法与分子对接技术研究灭幽汤异病同治慢性萎缩性胃炎和胃溃疡的作用机制。运用TCMSP和BATMAN-TCM数据库筛选出灭幽汤的有效成分,Genecards、OMIM、Disgenet、Drugbank数据库筛选出慢性萎缩性胃炎和胃溃疡的相关靶点;采用Cytoscape 3.9.1软件绘制“方剂-药物-活性成分-核心靶点-疾病”的网络拓扑图;采用STRING数据库构建蛋白互作网络;运用David数据库对核心靶点进行GO富集分析及KEGG通路分析;采用Auto Dock4软件进行分子对接预测药物与疾病靶点的结合性,通过Py MOL2.2软件实现对接结果可视化。结果得到灭幽汤有效成分73个, CAG相关靶点761个, GU相关靶点640个,通过Venny图取交集后得到54个靶点, Cytoscape筛选后得核心靶点37个。分子对接结果显示,TP53、IL6等5种蛋白与木犀草素(luteolin)、金合欢素(acacetin)、柚皮素(naringenin)、黄芩苷(baicalein)、汉黄芩素(wogonin)有较好的结合活性;KEGG富集分析主要得到癌症通路、脂质与动脉粥样硬化、PI3K-Akt信号通路、MAPK信号通路、IL-17信号通路、AGE-RAGE信号通路等。研究表明,灭幽汤异病同治慢性萎缩性胃炎和胃溃疡具有多成分、多靶点及多通路的特性,其主要成分与活性分子靶点结合,通过调控癌症、脂质与动脉粥样硬化等信号通路实现“同治”CAG和GU的目的。为传统中医药的“异病同治”理论提供了现代医学证据,并且为今后的新药研发与实验设计指明了方向。In this study,we employed a network pharmacology-molecular docking-based strategy to investigate the mechanism of Mie-you decoction(MYT)in treating chronic atrophic gastritis(CAG)and gastric ulcer(GU)based on the theory of“homotherapy for heteropathy”.First,we searched for the bioactive ingredients of MYT using the TCMSP and BATMAN-TCM databases.Then,we identified the corresponding protein targets for CAG and GU by searching the GeneCards,OMIM,DisGeNET,and DrugBank databases.Using Cytoscape 3.9.1,we constructed a“drug-ingredients-target-pathway-disease”network.The protein-protein interaction(PPI)network was generated using the STRING network platform.To further analyze the core targets,we performed Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses using the DAVID online tool.AutoDock4 was utilized to assess the binding affinity between ingredients and core targets,and the molecule-protein interactions were visualized using PyMOL 2.2.Our findings revealed a total of 73 bioactive ingredients with 101 potential targets for MYT.Among them,54 potential targets were identified for both CAG and GU.Ultimately,37 proteins were determined to be the core targets of MYT in combating CAG and GU.Molecular docking analysis demonstrated high affinity between five proteins,including tumor suppressor protein p53(TP53)and interleukin-6(IL-6),and bioactive ingredients,such as luteolin,acacetin,naringenin,baicalein,and wogonin.KEGG pathway enrichment analysis revealed 152 signaling pathways that might play crucial roles in the effectiveness of MYT against CAG and GU.The characteristics of MYT,including its multi-component,multi-target,and multi-pathway effects,aligned with the concept of“homotherapy for heteropathy”in both CAG and GU.By effectively modulating various signaling pathways,including those related to cancer,lipid metabolism,atherosclerosis,and others,MYT achieved its therapeutic objectives.These findings provided modern medical evidence supporting traditional Chinese

关 键 词：网络药理学 分子对接 慢性萎缩性胃炎 胃溃疡 异病同治 灭幽汤 

分 类 号：R961.1[医药卫生—药理学]