基于网络药理学探究香砂枳术丸治疗功能性消化不良的作用机制与实验验证  

Action Mechanism of Xiang Sha Zhi Zhu Wan in the Treatment of Functional Dyspepsia Based on Network Pharmacology and Experimental Verification

作　　者：李雪岩 罗志强 韩星 杨文宁[1] 陈洪娇 江晓泉 森慕黎 汪国鹏 刘洋[1] LI Xueyan;LUO Zhiqiang;HAN Xing;YANG Wenning;CHEN Hongjiao;JIANG Xiaoquan;SEN Muli;WANG Guopeng;LIU Yang(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China;School of Life Sciences,Beijing University of Chinese Medicine,Beijing 102488,China;Zhongcai Health(Beijing)Biological Technology Development Co.Ltd.,Beijing 101503,China)

机构地区：[1]北京中医药大学中药学院,北京102488 [2]北京中医药大学生命科学学院,北京102488 [3]中财瀚熙〔北京〕生物科技发展有限公司,北京101503

出　　处：《世界中医药》2023年第16期2280-2288,共9页World Chinese Medicine

基　　金：国家自然科学基金项目(81973295)。

摘　　要：目的:借助网络药理学的研究思路,探寻香砂枳术丸(XSZZW)治疗功能性消化不良(FD)的作用机制,并使用动物实验进行验证。方法:使用中药系统药理学数据库与分析平台(TCMSP)和中药分子机制生物信息学分析工具(BATMAN-TCM)筛选活性成分和靶点,借助Perl语言与UniProt将靶点进行标准化;通过TTD、DrugBank、OMIM以及GeneCards数据库筛选FD相关靶点;利用Cytoscape构建“中药复方-活性成分-作用靶点”网络;使用STRING数据库分别构建活性成分和疾病相关靶点蛋白质-蛋白质相互作用(PPI)网络并导入Cytoscape软件,以度值、接近中心性和介度中心性为条件筛选核心靶点;将核心靶点映射到DAVID数据库,进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)通路富集分析。最后,使用分子对接和动物实验进行结果验证。结果:获得活性成分75个以及靶点292个,FD相关的疾病靶点666个,经筛选最终获得核心靶点90个;GO富集分析主要在同源蛋白结合、酶结合、蛋白结合等生物学调控方面;KEGG富集分析得到信号通路103条,主要涉及癌症、细胞凋亡、炎症通路等方面。结论:香砂枳术丸可通过调控PI3K-AKT、FoxO、核因子κB、神经营养因子信号通路来预防或治疗FD。Objective:The action mechanism of Xiang Sha Zhi Zhu Wan(XSZZW)in the treatment of functional dyspepsia(FD)was explored by network pharmacology and verified by animal experiments.Methods:The effective components and targets of XSZZW were screened through traditional Chinese medicines systems pharmacology platform(TCMSP)and a bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine(BATMAN-TCM).The targets of components were standardized by the Perl language and the Uniprot database.The target of FD was screened by the Genecards,OMIM,Drugbank,as well as TTD databases.By using Cytoscape,the network of Chinese medicine-effective components-corresponding targets was constructed.The protein-protein interaction(PPI)networks of corresponding targets of effective components of XSZZW and FD-related targets were constructed by STRING database,respectively.Then,the PPI networks were imported to Cytoscape.Based on the values of degree,closeness centrality,and betweenness centrality,key targets were collected and mapped to the DAVID database.Gene ontology(GO)enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were conducted in the DAVID database.Finally,the results were validated by molecular docking and animal experiments.Results:A total of 75 effective components of XSZZW,292 corresponding targets,666 FD-related targets,and 90 key targets were obtained finally.GO enrichment analysis mainly included identical protein binding,enzyme binding,protein binding,and other biological regulation.103 pathways were enriched by KEGG analysis,mainly related to cancer,apoptosis,inflammation pathways,and other pathways.Conclusion:XSZZW can prevent and treat FD by regulating PI3K/AKT signaling pathways,FoxO signaling pathways,NF-κB signaling pathways,and neurotrophic factor signaling pathways.

关 键 词：香砂枳术丸 功能性消化不良 网络药理学 作用机制 分子对接 同源蛋白结合 细胞凋亡 炎症通路 

分 类 号：R285[医药卫生—中药学]