基于网络药理学分析葛根山楂人参颗粒解酒保肝的作用机制

Study on the Mechanism of Anti-alcoholism and Protecting Liver of Gegen Hawthorn Ginseng Granules Based on Network Pharmacology

葛根山楂人参颗粒是新开发研究的一款解酒护肝保健食品本文通过动物实验和网络药理学方法分析葛根山楂人参颗粒解酒保肝的作用机制。将40只小鼠随机分为空白组、模型组、阳性药组和葛根山楂人参颗粒组,连续给药10 d,最后1 d,除空白组以外的其余各组按照12mL·kg^(-1)的剂量灌胃56°白酒,建立急性酒精性肝损伤模型,并测定其肝组织中MDA、GSH和TG的含量,利用中草药系统药理学平台TCMSP、中医药百科全书数据库ETCM、PubChem及Swiss Target Prediction等数据库检索葛根山楂人参颗粒中6味中药的活性成分及相关靶点;通过GeneCards、OMIM、Drugbank及PharmGkb数据库获取酒精性肝病相关靶点;采用Cytoscape3.7.2软件进行网络构建与分析;利用功能关联蛋白网络数据库STRING和Cytoscape的Network Analyzer模块构建蛋白相互作用关系;通过基因注释工具(Metascape)进行基因本体分析和相关基因通路富集分析,将关键成分与靶点借助AutoDock软件进行分子对接验证。结果显示,筛选得到葛根山楂人参颗粒的活性成分59个,作用于956个靶点,酒精性肝病相关靶点有101个,主要发挥作用的靶点因子有糖皮质激素受体(NR3C1)、转录因子NFKB1、酪氨酸激酶(SRC)、类视黄醇X受体(RXRA)、蛋白激酶(AKT1)、核受体辅酶激活蛋白2(NCOA2)、过氧化物酶体增生激活受体(PPARG)、雌激素受体(ESR1)和雄激素受体(AR)等;其主要作用的通路有类固醇激素生物合成、癌症的途径、EB病毒感染、甲状腺激素和胆汁分泌异常等。动物实验揭示了葛根山楂人参颗粒具有解酒保肝的作用,结合网络药理学及分子对接技术,为其治疗酒精性肝病的研究和临床应用提供了新的思路和方法。

Gegen Hawthorn Ginseng granules is a newly developed health food for relieving alcoholism and protecting liver,in this study,the network pharmacology and animal experiments were used to analyze the mechanism of Gegen Hawthorn Ginseng Granules in relieving alcoholism and protecting liver.40 mice were randomly divided into blank group,model group,positive drug group,pueraria hawthorn ginseng particle group,administered continuously for 10 days,the last day,the remaining groups other than the blank group was given 56 according to the dosage 12 mg·kg^(-1) of liquor,establishing an acute alcohol injury model.Determination of liver tissue MDA,GSH,TG content.Using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP,The Encyclopedia of Traditional Chinese Medicine,ETCM,PubChem,Swiss Target Prediction,and others.Targets related to liver diseases were obtained from the GeneCards,OMIM,Drugbank,and PharmGkb databases.Network construction and analysis were performed using Cytoscape software.The protein-protein interaction relationship was constructed using the Functional Protein Association Networks(STRING)and Cytoscape’s Network Analyzer module.To predict its action mechanism,Gene Ontology analysis and Kyoto encyclopedia of genes and genes pathway enrichment analysis were performed by Metascape.AutoDock Vina 4.0 was used to conduct molecular docking verification library for key target components and analyze the gene function and pathway of target proteins.With the help of AutoDock software,molecular docking verification of key components and important targets was performed.The result showed that Fifty-nine active components of Gegen Hawthorn Ginseng granules were screened,which acted on 956 targets,101 of which were involved in alcoholic liver disease.The main action targets are glucocorticoid receptor(NR3 C1),transcription factor NFKB1,tyrosine kinase(SRC),retinoid X receptor(RXRA),protein kinase(AKT1),nuclear receptor coactivator protein 2(NCOA2),peroxisome proliferator-activated receptor(PPARG),estrogen receptor(ESR1)and andro gen receptor(AR).The predicted target mainly plays a role in the liver protection of steroid hormone biosynthesis,cancer pathway,Epstein-Barr virus infection,thyroid hormone signaling pathway,abnormal bile secretion and other pathways.Animal experiments revealed that the Gegen Hawthorn Ginseng Granules can relieve alcohol and protect the liver,combined with network pharmacology and molecular docking technology,which would provides a new thought and method for the treatment of alcoholic liver disease research and clinical application.