基于网络药理学和动物实验探讨青皮-枳壳药对治疗动力障碍型胃肠疾病的配伍关系  

Compatibility relationship of Citri Reticulatae Pericarpium Viride-Aurantii Fructus drug pair in the treatment of dyskinetic gastrointestinal diseases based on network pharmacology and animal experiments

作　　者：宁芯誉 罗雯雯 李吉旺 陈东良 仇曌松 林志岭 柳贤福[2] NING Xin-yu;LUO Wen-wen;LI Ji-wang;CHEN Dong-liang;CHOU Zhao-song;LIN Zhi-ling;LIU Xian-fu(Graduate School,Guangxi University of Chinese Medicine;Faculty of Chinese Medicine Science Guangxi University of Chinese Medicine,Nanning 530200,China)

机构地区：[1]广西中医药大学研究生院 [2]广西中医药大学赛恩斯新医药学院,南宁530200

出　　处：《天然产物研究与开发》2024年第12期2133-2144,共12页Natural Product Research and Development

基　　金：国家级大学生创新创业训练计划(202413643015);广西中医药大学赛恩斯新医药学院校级课题(2024MS005)。

摘　　要：基于网络药理学及动物实验探讨青皮-枳壳药对治疗动力障碍型胃肠疾病的配伍关系。利用青皮-枳壳与胃肠疾病的交集靶点构建蛋白质-蛋白质相互作用网络图并进行富集分析,选取“靶点-成分-通路”图中中介中心性值前5的关键靶点与其相应的活性成分进行分子对接;以小鼠的体重、胃残留率与血清胃动素浓度为指标,观察青皮-枳壳(1∶1、1∶2、2∶1)与其单味药治疗L-精氨酸溶液引起的小鼠胃肠动力障碍的差异。网络药理学的结果显示青皮-枳壳治疗胃肠疾病的核心靶点有CYP2C9、EGFR和HSD11B1;核心成分有β-谷甾醇、甜橙黄酮、柚皮素、新橙皮苷、橙皮素、马尔敏、百里酚、川陈皮素和5,7-二羟基-2-(3-羟基-4-甲氧基苯基)铬-4-酮;核心靶点与核心成分对接良好。动物实验的结果表明单行和配伍使用的青皮-枳壳均能改善小鼠胃肠运动障碍;配伍组的疗效优于单味药组,其中青枳1∶2组优于青枳1∶1组与青枳2∶1组。本研究初步揭示青皮-枳壳治疗动力障碍型胃肠疾病的最佳配伍比与作用机制,为青皮-枳壳治疗胃肠疾病的进一步研究提供参考依据。This study aims to explore the compatibility relationships of Citri Reticulatae Pericarpium Viride-Aurantii Fructus drug pair(CV-AF)in the treatment of dyskinetic gastrointestinal diseases(GD)based on network pharmacology and animal experiments.The intersection targets between CV-AF and GD were used for the chart construction and enrichment analysis of protein-protein interactions;and the key targets of the top 5 betweenness centrality values in the“target-component-pathway”chart were selected for molecular docking with their corresponding components;the body weight,gastric residual rates,and serum motilin concentrations of mice were used as indicators to observe the differences between CV-AF(1∶1,1∶2,2∶1)and their corresponding single drug for the treatment of gastrointestinal dyskinesia in mice induced by L-arginine solution.The results of network pharmacology showed that the core targets of CV-AF for the treatment of GD were CYP2C9,EGFR,and HSD11B1;the core components wereβ-sitosterol,sinensetin,naringenin,neohesperidin_qt,hesperetin,marmin,thymol,nobiletin,and 5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one;the core targets were well combined with the core components.The results of animal experiments indicated that both individual and combined use of CV-AF ameliorated gastrointestinal dyskinesia of mice;the efficacy of CV-AF groups was better than their corresponding single drug groups,with the CV-AF 1∶2 group being better than the CV-AF 1∶1 group and the CV-AF 2∶1 group.This study reveals the optimal pairing ratio and action mechanism for the treatment of dyskinetic GD by CV-AF preliminary,which can provide a reference basis for further research on the treatment of GD by CV-AF.

关 键 词：网络药理学 分子对接 动物实验 药对 青皮-枳壳 胃肠疾病 

分 类 号：R285.5[医药卫生—中药学]