基于网络药理学及实验验证探讨良附丸治疗功能性消化不良的作用机制  

Mechanism of Liangfu Pills in treatment of functional dyspepsia: based on network pharmacology and experimental verification

作　　者：何杰滢 桂蓓 陈艳芬 尹永芹 陶曙红 沈志滨 李坤平 付江波 魏玲 HE Jie-ying;GUI Bei;CHEN Yan-fen;YIN Yong-qin;TAO Shu-hong;SHEN Zhi-bin;LI Kun-ping;FU Jjiang-bo;WEI Ling(School of Traditional Chinese Medicine,Guangdong Pharmaceutical Universily,Guangzhou 510006,China;Institue of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou 510006,China)

机构地区：[1]广东药科大学中药学院,广东广州510006 [2]广东药科大学中医药研究院,广东广州510006

出　　处：《中国中药杂志》2022年第14期3853-3862,共10页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81302894)。

摘　　要：采用网络药理学方法及分子对接技术探析良附丸治疗功能性消化不良(functional dyspepsia, FD)潜在的作用机制,并通过动物实验研究良附丸对FD大鼠的干预作用及机制。利用TCMSP数据库(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform)获取和筛选良附丸的活性成分,利用SwissTargetPrediction数据库预测药物的作用靶点,通过GeneCards数据库检索FD相关靶点;药物与疾病靶点相交集后,导入STRING数据库检索蛋白互作关系,筛选关键靶点,利用DAVID数据库进行GO(Gene Oncology)生物过程分析和KEGG(Kyoto Encyclopedia of Genes and Genomes)通路富集分析,最后借助AutoDock Tools软件进行分子对接,预测良附丸有效成分与关键靶点的结合度。网络药理学筛选出良附丸的活性成分19个及与FD相关的靶点591个,其中交集靶点253个;GO和KEGG富集分析发现良附丸主要与药物反应、转录的负调控、细胞凋亡的正调控、细胞表面受体信号通路等生物过程有关,富集在HIF-1信号通路、5-羟色胺能突触、TNF信号通路、cAMP信号通路、钙信号通路、TRP通道的炎症介质调节等。分子对接结果显示良附丸关键有效成分与靶点MAPK1、AKT1、TRPV1、HTR1A、HTR2A均有一定的结合活性。动物实验构建FD大鼠模型,造模成功后给予良附丸治疗7 d,检测结果显示,良附丸组能显著缓解FD大鼠的症状,且明显升高5-HT的表达水平,下调TRPV1的表达。通过网络药理学、分子对接分析和实验验证,证明良附丸对功能性消化不良的改善具有多成分、多靶点的特点,为进一步的良附丸治疗功能性消化不良机制研究及临床应用提供了依据。This study aims to explore the potential mechanism of Liangfu Pills in the treatment of functional dyspepsia(FD) based on network pharmacology and molecular docking, and verify the mechanism by animal experiment. The active components of Liangfu Pills were screened from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets of Liangfu Pills were predicted by SwissTargetPrediction. The targets of FD were retrieved from GeneCards. On this basis, the common targets of the disease and the pills were yielded and the protein interaction was retrieved based on STRING. The core targets were screened out, followed by Gene Oncology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis with DAVID. Finally, molecular docking was carried out with the help of AutoDock Tools to predict the binding degree between the effective components of Liangfu Pills and core targets. A total of 19 active components of Liangfu Pills and 591 FD-related targets were screened out by network pharmacology, of which 253 were common targets of the disease and the prescription. Liangfu Pills was mainly involved in the biological processes of response to drug, negative regulation of transcription, positive regulation of apoptotic process, and cell surface receptor signaling pathway, and the KEGG pathways of hypoxia-inducible factor-1(HIF-1) signaling pathway, serotonergic synapse, tumor necrosis factor(TNF) signaling pathway, cyclic adenosine monophosphate(cAMP) signaling pathway, calcium signal pathway, and inflammatory mediator regulation of transient receptor potential(TRP) channels. The results of molecular docking showed that the key active components of Liangfu Pills had certain binding activity to the targets mitogen-activated protein kinase 1(MAPK1), protein kinase B(AKT1), transient receptor potential cation channel subfamily V member 1(TRPV1), 5-hydroxytryptamine receptor 1 A(HTR1 A), and 5-hydroxytryptamine receptor 2 A(HTR2 A). FD was induced in

关 键 词：良附丸 功能性消化不良 网络药理学 分子对接 作用机制 动物实验 

分 类 号：R285[医药卫生—中药学]