基于网络药理学与分子对接技术的菊苣抗高尿酸血症作用机制研究

Study on the mechanism of chicory against hyperuricemia based on network pharmacology and molecular docking

运用网络药理学与分子对接技术研究菊苣抗高尿酸血症的主要活性成分及作用机制.通过TCMSP收集菊苣的化学成分及靶点并使用Uniprot进行筛选,建立"菊苣有效成分-靶点数据库".在GeneCards、Drugbank、Disgenet及OMIM数据库中搜集高尿酸血症靶点,预测菊苣中抗高尿酸血症的活性成分的潜在作用靶基因.用Cytoscape3.8.0软件构建菊苣的"药物-活性成分-作用靶点"可视化网络.在STRING中导入预测靶点,并构建菊苣治疗高尿酸血症靶点的PPI网络.用R语言中"clusterProfiler"安装包进行GO功能富集和KEGG通路分析,采用AutoDockVina进行分子对接.经筛选共得菊苣活性成分10个.共预测到活性靶点98个,疾病靶点860个,去重结合得疾病靶点菊苣抗高尿酸血症潜在作用靶点39个,构建PPI网络分析得核心靶点有TP53、IL6、TNF等.GO富集分析结果77条,KEGG分析结果127条,主要涉及细胞因子受体结合、细胞因子活性等生物过程,通过IL17和AGE-RAGE信号通路发挥作用.分子对接结果为木犀草素和β-谷甾醇与靶蛋白亲和力最好.菊苣中的多种活性成分如木犀草素、β-谷甾醇等可能通过TP53、IL6、JUN、CASP3和TNF等靶点对信号通路进行调控,涉及多种生物过程,从而发挥抗高尿酸血症的疗效.

Based on network pharmacology and molecular docking technology,the active components and mechanism of chicory for preventing and treating hyperuricemia were studied.The chemical constituents and targets of chicory were collected by Traditional Chinese Medicine Systems Pharmacology Database(TCMSP)and screened by Uniprot to establish the database of chicory active constituents and targets.Through Genecards,Drugbank,Disgenet and OMIM databases,the overlapping genes of active components and hyperuricemia were collected.The visualization network of"drug-compounds-targets"of chicory was constructed by Cytoscape3.8.0 software.String database was used for protein-protein interaction network(PPI)analysis.The"clusterProfiler"installation package in R language was used for GO function enrichment and KEGG pathway analysis,and AutodockVina was used for molecular docking.Twelve components of chicory were involved.98 active targets and 860 disease targets were predicted,and 39 potential targets of chicory were obtained.And the core targets of PPI network analysis were TP53,IL6,TNF,etc.GO enrichment analysis showed 77 and KEGG analysis showed 127 signal pathways,which mainly involved in signaling pathways such ascytokine receptor binding and cytokine activity,through IL17 and AGE-RAGE signaling pathway.The results of molecular docking showed that the affinity between luteolin,β-sitosterol and target protein was the best.There were many active ingredients in chicory,such as luteolin.β-sitosterol may regulate the signaling pathway through TP53,IL6,JUN,CASP3 and TNF,involving a variety of biological processes,so as to play the role of preventing and treating hyperuricemia.