栀黄止痛颗粒治疗痛风性关节炎作用机制的网络药理学及分子对接技术研究  

Study on Network Pharmacology and Molecular Docking of Zhihuang Zhitong Granules in the Treatment of Gouty Arthritis

作　　者：刘畅[1] 许博 孟庆良[1] 郭克磊 卞华 Liu Chang;Xu Bo;Meng Qingliang;Guo Kelei;Bian Hua(The Second Affiliated Hospital of Henan University of Chinese Medicine,Henan,Zhengzhou 450002,China)

机构地区：[1]河南中医药大学第二附属医院,河南郑州450002 [2]南阳理工学院张仲景国医国药学院,河南省张仲景方药与免疫调节重点实验室,河南南阳473004

出　　处：《中国中医急症》2024年第5期763-768,共6页Journal of Emergency in Traditional Chinese Medicine

基　　金：国家自然科学基金项目(82074415);中原英才计划-中原科技创新领军人才项目(234200510006);河南省科技攻关(232102311201)。

摘　　要：目的通过网络药理学和分子对接技术研究栀黄止痛颗粒治疗痛风性关节炎(GA)的科学原理及作用机制。方法通过HERB数据库查找栀黄止痛颗粒的主要活性成分和作用靶点,利用UniProt数据库进行靶点名称规范及转化,通过GeneCards、OMIM、PharmGkb、TTD、DrugBank数据库总结GA相关疾病靶点,将疾病靶点与药物靶点取交集,利用Cytoscape3.8.0软件生成“药物-活性成分-靶点网络”,通过STRING数据库构建交集靶点的蛋白相互作用网络,使用Cytoscape进行拓扑分析,获得核心基因;运用Metascape网页、R软件构建的数据包对核心基因进行基因本体(GO)功能和基因组数据库(KEGG)通路富集分析,最后选取核心靶点与药物活性成分进行分子对接验证。结果筛选出栀黄止痛颗粒活性成分88种,作用靶点212个;GA疾病靶点312个,疾病与药物交集靶点43个。GO富集分析共包含56条富集通路,其中生物过程4条、分子功能21条、细胞组成31条;KEGG通路富集分析得到133条通路,涉及脂质和动脉粥样硬化、IL-17信号通路、糖尿病并发症中的AGE-RAGE信号通路、TNF信号通路、流体剪切应用与动脉粥样硬化等通路。分子对接结果表明药物主要活性成分与核心基因之间能相互结合并有较好的亲和力。结论栀黄止痛颗粒是通过多成分、多靶点、多途径对GA产生药理作用,这为探索该方剂药效药理作用机制建立了基础。Objective:To investigate the scientific principle and mechanism of Zhihuang Zhitong Granules in the treatment of gouty arthritis(GA)based on network pharmacology and molecular docking technology.Methods:The main active ingredients and targets of Zhihuang Zhitong Granules were searched through HERB database,and target names were regulated and transformed using Uniprot database.GA-related disease targets were summarized through GeneCards,OMIM,PharmGkb,TTD and DrugBank databases,and the intersection of disease targets and drug targets was selected.Cytoscape software 3.8.0 was used to generate drug-active ingredient and target network,and the protein interaction network of intersecting targets was constructed using STRING database.Topological analysis was carried out on Cytoscape software to obtain core genes.The data package constructed by Metascape web page and R software was used for gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of core genes.Finally,core targets were selected for molecular docking veri⁃fication with active pharmaceutical ingredients.Results:A total of 88 active components of Zhihuang Zhitong Granules were screened,and 212 targets were identified.GA had 312 disease targets and 43 disease and drug in⁃tersection targets.A total of 56 enrichment pathways were included in GO enrichment analysis,including 4 biologi⁃cal processes,21 molecular functions and 31 cell compositions.KEGG pathway enrichment analysis revealed 133 pathways,involving lipid and atherosclerosis,IL-17 signaling pathway,AGE-RAGE signaling pathway in diabetes complications,TNF signaling pathway,fluid shear application and atherosclerosis pathways.The results of molecular docking showed that the main active components of the drug and the core genes could bind to each other and had good affinity.Conclusion:Zhihuang Zhitong Granules has pharmacological effects on GA through multiple components,multiple targets,multiple ways,which lays a foundation for exploring the pharmacolo

关 键 词：痛风性关节炎 栀黄止痛颗粒 网络药理学 分子对接 作用机制 

分 类 号：R589.7[医药卫生—内分泌]