基于网络药理学和分子对接探讨独活寄生汤治疗骨质疏松症的作用机制  

Action Mechanism of Duhuo Jisheng Decoction in Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking

作　　者：吴成强[1] 许京伟 王静 李海涛 张守庆 吴亚东[1] WU Chengqiang;XU Jingwei;WANG Jing;LI Haitao;ZHANG Shouqing;WU Yadong(Rizhao Hospital of Traditional Chinese Medicine,Rizhao Shandong China 276800)

机构地区：[1]日照市中医医院,山东日照276800

出　　处：《中医学报》2023年第8期1739-1746,共8页Acta Chinese Medicine

基　　金：山东省中医药科技项目面上项目(M-2022092);山东省自然科学基金项目(ZR2021LZY006)。

摘　　要：目的:应用网络药理学及分子对接分析独活寄生汤治疗骨质疏松症(osteoporosis,OP)的作用机制。方法:通过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)获得独活寄生汤组方中药的化学成分;在SwissTargetPrediction数据库预测获得独活寄生汤各有效成分对应靶点,并利用Cytoscape 3.7.8软件构建“药物-有效成分-靶点”网络。在治疗靶点数据库、DrugBank数据库、GeneCards数据库及Disgenet数据库检索OP相关靶点;将有效成分对应靶点及疾病靶点映射取交集,获得共同靶点,即为独活寄生汤治疗OP的潜在靶点,并应用Funrich软件绘制韦恩图。将潜在靶点录入string数据库,绘制PPI网络图,并进行分析筛选得到核心靶点。将潜在靶点导入Metascape软件进行基因本体(gene ontology,GO)富集分析及京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)信号通路富集分析。选择核心靶点作为分子对接受体,相关对应有效成分为配体进行分子对接,并进行Pymol可视化展示。结果:根据TCMSP数据库获得独活寄生汤有效化合物194个,对应靶点575个。在治疗靶点数据库及DrugBank、GeneCards、Disgenet数据库得到840个OP相关靶点,将有效成分预测的靶点与疾病靶点映射获得共同靶点105个。PPI网络分析得到EGFR、ESR1、AKT1、INS、VEGFA、TNF、SRC、MMP9、JUN、STAT3、FGF2共11个关键靶点。GO富集分析得到分子功能150条,细胞组分62条,生物学过程1296条。KEGG富集分析得到98条信号通路。独活寄生汤中部分化合物与关键靶点蛋白分子结合良好。结论:独活寄生汤可能通过TNF、JUN、AKT1、SRC、GF2等靶点作用于雌激素信号通路、肿瘤坏死因子信号通路等调控破骨细胞的分化、干细胞多能性、类固醇代谢等干预治疗骨质疏松症。Objective:To analyze the mechanism of action of Duhuo Jisheng Decoction in treatment of osteoporosis(OP)by network pharmacology and molecular docking.Methods:The chemical components of traditional Chinese medicine formulated by traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)were obtained.In the SwissTargetPrediction database,the corresponding targets of each active ingredient of the solo parasitic soup were predicted,and the"drug-active ingredient-target"network was constructed by using Cytoscape 3.7.8 software.Search OP-related targets in therapeutic target database,DrugBank database,GeneCards database and Disgenet database;The corresponding targets of the active ingredients and the disease targets were mapped and intersected to obtain the common target,that is,the potential target of the OP of Duhuo Jisheng Decoction,and the Wayne diagram was drawn by Funrich software.The potential targets were entered into the string database,the PPI network diagram was drawn,and the core targets were obtained by analysis and screening.Potential targets were introduced into Metascape software for gene ontology(GO)enrichment analysis and kyoto encyclopedia of genes and genomes(KEGG)signaling pathway enrichment analysis.The core target was selected as the molecular pair acceptor,and the relevant corresponding active ingredient was the ligand for molecular docking,and Pymol visualization was performed.Results:According to the TCMSP database,194 effective compounds of solo live parasitic decoction were obtained,corresponding to 575 targets.840 relevant targets were obtained in TTD,DrugBank,GeneCards and Disgenet databases,and 105 common targets were obtained by mapping targets predicted by active ingredients with disease targets.PPI network analysis yielded 11 key targets including EGFR,ESR1,AKT1,INS,VEGFA,TNF,SRC,MMP9,JUN,STAT3 and FGF2.GO enrichment analysis yielded 150 molecular functions,62 cellular components,and 1296 biological processes(BP).KEGG enrichment analysis yielded 98 signal p

关 键 词：独活寄生汤 骨质疏松症 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]