基于网络药理学及分子对接技术挖掘枳实理气功效治疗功能性便秘的作用机制  

Regulating Qi Mechanism of Poncirus Aurantii for Functional Constipation Based on Network Pharmacology and Molecular Docking Techniques

作　　者：康婕 隋楠[2] KANG Jie;SUI Nan(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;The Third flicted Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110003,Liaoning,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属第三医院,辽宁沈阳110003

出　　处：《实用中医内科杂志》2025年第4期46-51,I0010-I0014,共11页Journal of Practical Traditional Chinese Internal Medicine

基　　金：国家自然科学基金项目(82174370)。

摘　　要：目的运用网络药理学与分子对接探究枳实理气作用治疗功能性便秘的关键有效成分及作用靶点及通路,探索枳实可能的药效物质基础及潜在的分子机制。方法通过TCMSP、PubChem、SwissADME等数据库对枳实主要活性成分及相关作用靶点进行筛选收集。基于GeneCards数据库检索理气、功能性便秘相关靶点,将理气靶点、功能性便秘靶点与枳实这一味药的作用靶点进行映射,得出枳实理气功效治疗功能性便秘的功效靶点,依托STRING数据库构建蛋白相互作用(PPI)网络,将结果通过Cytoscape 3.10.1进行可视化。通过DAVID数据库进行GO与KEGG通路富集分析。筛选出枳实这一味药的关键活性化合物和靶基因后,进行分子对接,预测活性化合物与核心靶点的结合,得出其可能作用的分子机制并构建“化合物–靶点–通路”网络图。结果枳实中共有19个活性成分和1823个相应靶点,GeneCards数据库中共筛选出1313个理气相关的靶点信息,1011个功能性便秘相关的靶点信息。最终筛选获得120个核心靶点和165个信号通路,包括磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)信号通路、MAPK信号通路、EGFR酪氨酸激酶抑制剂抵抗通路等。枳实具有理气功效治疗功能性便秘的主要成分为木犀草素、柚皮素、异橙黄酮、川陈皮素和橙皮素,关键靶点为AKT1、PIK3CA、MAPK1、MAPK3等。分子对接显示木犀草素、柚皮素、川陈皮素分别与AKT1、PIK3CA、MAPK1、MAPK3结合良好。结论枳实中的木犀草素、柚皮素、异橙黄酮、川陈皮素和橙皮素可能为其发挥理气功效治疗功能性便秘的主要活性成分,同时,枳实能够通过多成分作用于多靶点,激活多条通路去治疗功能性便秘,其作用通路可能与PI3K-AKT信号通路,MAPK信号通路等有关,为日后枳实在临床上治疗功能性便秘地进一步研究提供了理论基础与科学依据。Objective Using network pharmacology and molecular docking to explore the key active ingredients,targets and pathways of Zhishi Liqi in the treatment of functional constipation,and to explore the possible pharmacodynamic material basis and potential molecular mechanism of Zhishi.Methods The main active components and their related targets were screened and collected by TCMSP,PubChem,SwissADME and other databases.Based on GeneCards database,related targets of regulating qi and functional constipation were retrieved,and the targets of regulating qi and functional constipation were mapped with those of trifoliate,a blind drug,to obtain the effective targets of Zhishi Liqi in treating functional constipation.The protein interaction(PPI)network was constructed based on STRING database.Visualize the results via Cytoscape 3.10.1.GO and KEGG path enrichment analysis was performed using DAVID database.The key active compounds and target genes of Trifoliate were screened,molecular docking was carried out to predict the binding of active compounds and core targets,the molecular mechanism of their possible action was obtained,and the network diagram of"compound-target-pathway"was constructed.Results There were 19 active ingredients and 1823 corresponding targets in Fructus aurantii.1313 target information related to regulating qi and 1011 target information related to functional constipation were selected in GeneCards database.Finally,120 key targets and 165 signaling pathways were obtained,including phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway,MAPK signaling pathway,EGFR tyrosine kinase inhibitor resistance pathway,etc.The main components of trifoliate in treating functional constipation are luteolin,naringin,isohesperetin,tangerine and hesperetin,and the key targets are AKT1,PIK3CA,MAPK1,MAPK3 and so on.Molecular docking showed that luteolin,naringin and tetraceolin were well combined with AKT1,PIK3CA,MAPK1 and MAPK3,respectively.Conclusion Luteolin,naringin,isohesperetin,tangerine and hespere

关 键 词：枳实 理气 功能性便秘 网络药理学 分子对接 木犀草素 

分 类 号：R285[医药卫生—中药学]