基于网络药理学和分子对接技术研究四妙勇安汤治疗痛风性关节炎的作用机制  

Mechanism of Simiao Yong’an Decoction in the Treatment of Gout Arthritis Based on Network Pharmacology and Molecular Docking Technology

作　　者：江厚辰 徐逸生[1] 张葆青[1] 肖方骏 陈文治[2] JIANG Houchen;XU Yisheng;ZHANG Baoqing;XIAO Fangjun;CHEN Wenzhi(Second Clinical Medical College,Guangzhou University of Chinese Medicine,Guangdong Guangzhou 510120,China;Dept.of Orthopedics,Fangcun Branch Hospital of Guangdong Hospital of Traditional Chinese Medicine,Guangdong Guangzhou 510120,China)

机构地区：[1]广州中医药大学第二临床医学院,广东广州510120 [2]广东省中医院芳村分院骨伤科,广东广州510120

出　　处：《中国医院用药评价与分析》2021年第11期1320-1326,共7页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：广东省中医院刘金文学术经验传承工作室专项基金支持项目(粤中医办函〔2017〕17号)。

摘　　要：目的:运用网络药理学联合分子对接技术研究四妙勇安汤干预痛风性关节炎的相关靶点与信号通路,探讨四妙勇安汤治疗痛风性关节炎的分子作用机制。方法:在中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)中筛查出四妙勇安汤组方中的4味中药的活性成分与作用靶点,然后在人类孟德尔遗传综合数据库(online mendelian inheritance in man,OMIM)、GeneCards、PharmGkb、DrugBank和治疗靶点数据库(therapeutic target database,TTD)等数据库中筛选出痛风性关节炎的相关基因靶点,整合后获取药物靶点与疾病靶点的共同交集,并借助Cytoscape 3.7.2软件拓扑出“活性成分-核心靶点”网络图,通过STRING在线数据库平台获取蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络图,并对所获得的关键靶点采用基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。通过Autodock 1.5.6软件对药物的主要活性成分及核心作用靶点进行分子对接匹配验证。结果:筛选得到四妙勇安汤干预痛风性关节炎的活性成分96个,靶点38个,其中主要活性成分有槲皮素、山柰酚、柚皮苷和木犀草素等,主要靶点为PTGS2、NOS2、PPARG、MAPK14和PTGS1等,PPI网络分析出CXCL8、PTGS2、MAPK3、TNF、IL-1β、CCL2、MAPK1和HMOX1等8个核心靶点。分子对接结果显示,四妙勇安汤的主要活性成分能够与核心靶点结合且展现出较好的亲和力。结论:四妙勇安汤治疗痛风性关节炎具有多途径、多组分和多靶点的机制特征,四妙勇安汤干预痛风性关节炎的潜在作用机制可能与其发挥降解尿酸、下调炎症因子的表达和调节免疫功能等作用相关。OBJECTIVE:To explore the related targets and signal pathways of Simiao Yong’an decoction intervening gout arthritis by using network pharmacology combined with molecular docking technology,so as to probe into the mechanism of Simiao Yong’an decoction in the treatment of gout arthritis.METHODS:The active ingredients and targets of four herbs in the formula of Simiao Yong’an decoction were screened out by the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),the related gene targets of gout arthritis were screened out by online mendelian inheritance in man(OMIM),GeneCards,PharmGkb,DrugBank and therapeutic target database(TTD),the common intersection of drug targets and disease targets were obtained after integration,and the network diagram of“active ingredient-core target”was topologized with the help of Cytoscape 3.7.2 software,the protein-protein interaction(PPI)network diagram was obtained through the STRING online database platform,and the gene ontology(GO)functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were used for the acquired key targets.Finally,the matching and validation of molecular docking on main active ingredients and core targets of the drug were conducted by using Autodock 1.5.6 software.RESULTS:Totally 96 active ingredients and 38 targets were screened out in the intervention of Simiao Yong’an decoction on gouty arthritis,including the main active ingredients of quercetin,kaempferol,naringenin and lignan,including the main targets of PTGS2,NOS2,PPARG,MAPK14 and PTGS1.The PPI network had analyzed 8 core targets including CXCL8,PTGS2,MAPK3,TNF,IL-1β,CCL2,MAPK1 and HMOX1.Results of the molecular docking indicated that the main active ingredients of Simiao Yong’an decoction could bind to the core targets and showed good affinity.CONCLUSIONS:The application of Simiao Yong’an decoction in the treatment of gouty arthritis has the characteristics of multiple pathways,multiple components and mu

关 键 词：四妙勇安汤 痛风性关节炎 网络药理学 分子对接 作用机制 

分 类 号：R932[医药卫生—生药学] R96[医药卫生—药学]