基于网络药理学及分子对接技术探讨桔梗联合枳壳治疗泌尿系结石的机制

Exploring potential mechanism of Platycodon combined with Zhike to treat urinary calculi by network pharmacology and molecular docking

目的利用网络药理学及分子对接技术挖掘桔梗联合枳壳药对治疗泌尿系结石的潜在机制。方法利用传统中药系统药理学数据库和分析平台(TCMSP)进行桔梗、枳壳中药活性成分分析及靶基因筛选。使用GeneCards、OMIM、TTD、Pharmgkb、Drugbank疾病数据库获得泌尿系结石相关基因。使用Cytoscape构建“成分-靶点”网络,使用CentiScape计算活性成分度值(DC)。使用STRING数据库下载蛋白与蛋白相互作用(PPI)数据,导入Cytoscape,使用CytoNCA插件处理获取核心靶基因。使用R软件进行相关靶基因基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。对活性成分及核心基因作分子对接。结果从桔梗、枳壳中共筛选12个活性成分,30个治疗泌尿系结石的靶基因,构建“成分-靶点”网络。筛选得出PPI核心靶基因共12个。GO功能富集显示在生物学功能方面,桔梗、枳壳主要参与G蛋白偶联受体活性、抗氧化活性等生物学过程。KEGG通路富集显示,桔梗、枳壳治疗泌尿系结石主要涉及肿瘤坏死因子(TNF)、白介素17信号通路(IL-17)、VEGF信号通路及雌激素信号通路等。分子对接结果提示luteolin(木犀草素)、nobiletin(蜜橘黄素)与核心蛋白(MAPK1、VEGFA、MMP9)结合能均≤-6 kcal/mol。结论桔梗、枳壳药对中木犀草素、蜜橘黄素等活性成分可从氧化应激、炎症反应、细胞损伤、性激素等多个途经防治泌尿系结石。

Objective To explore the potential mechanism of Platycodon combined with Zhike on the treatment of urinary calculi by network pharmacology and molecular docking.Methods Active ingredients and target genes of Platycodon and Zhike were screened through the Traditional Chinese Medicine system pharmacology database and analysis platform(TCMSP).Urinary calculi related genes were searched in GeneCards,OMIM,TTD,Pharmgkb,Drugbank disease database.A"component-target"network was constructed by Cytoscape.Protein-protein interaction(PPI)data were download from STRING database and imported into Cytoscape.The core target genes were obtained by CytoNCA plug-in.Enrichment analysis of related target genes(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were analyzed by R software.Active ingredients and core genes were performed by molecular docking.Results A total of 12 active ingredients were screened from Platycodon and Zhike,and 30 target genes for the treatment of urinary calculi,to construct a"compo-nent-target"network.A total of 12 PPI core target genes were screened.GO function enrichment shows that in terms of biological functions,Platycodon and Zhike are mainly involved in biological processes such as G protein-coupled receptor activity and antioxidant activity.Enrichment of KEGG pathway shows that treatment of urinary calculi by Platycodon and Zhike mainly involves tumor necrosis factor(TNF),interleukin 17 signaling pathway(IL-17),VEGF signaling pathway,and estrogen signaling pathway.The results of molecular docking indicated that the binding energy of luteolin,nobiletin and core proteins(MAPK1,VEGFA,MMP9)were all≤-6 kcal/mol.Conclusion Platycodon and Zhike are a drug pair,in which active ingredients such as quercetin can prevent and treat urinary calculi through multiple methods such as oxidative stress,inflammation,cell damage,sex hormones and so on.