基于网络药理学和分子对接分析探讨五苓散治疗肾结石的潜在作用机制

Network pharmacological study and molecular docking analysis on potential mechanism of Wuling Powder in treatment of kidney stone

目的:基于网络药理学和分子对接法探讨五苓散治疗肾结石的潜在分子机制。方法:利用中药系统药理学数据库和4个疾病基因数据库获取五苓散⁃肾结石共同靶点,利用Cytoscape version 3.8.0构建复合靶网络,GO和KEGG富集分析和蛋白质相互作用(PPI)网络分析发现其潜在分子机制。通过分子对接,观察有效分子与目标蛋白之间的相互作用模式。结果:通过分析五苓散药物相关靶点与肾结石靶点信息,取交集并绘制韦恩图,得到五苓散⁃肾结石共同靶点13个。构建了一个包含20个节点和19条关联线路的化合物靶基因相互作用网络,β⁃谷甾醇被认为是最有价值的化合物。通过PPI网络显示靶基因编码的蛋白具有复杂的相互作用,GO和KEGG提示五苓散可通过调控G蛋白偶联受体信号通路、钙信号通路和其他因素调控的钙重吸收而发挥作用。通过对最靶向的基因CHRM3进行分子对接,β⁃谷甾醇可进入CHRM3的活性口袋,对肾结石发挥潜在治疗作用。结论:G蛋白偶联受体信号通路、钙信号通路和其他因素调控的钙重吸收可能是五苓散治疗肾结石的潜在分子机制。β⁃谷甾醇可能是一种很有前途的治疗肾结石药物。

Objective:To investigate the potential mechanism of Wuling Powder in the treatment of kidney stone via network pharmacological study and molecular docking analysis.Methods:Wuling Powder⁃kidney stone intersected targets were obtained from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)and four disease⁃gene databases.Cytoscape 3.8.0 software was used to construct a traditional Chinese medicine(TCM)compound⁃target⁃disease network.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and protein⁃protein interaction(PPI)network were performed to determine the potential mechanism.Molecular docking was performed to identify the patterns of interactions between effective molecules and targeted proteins.Results:By analyzing the information of Wuling Powder⁃related targets and kidney stone targets,the intersection was obtained and the Venn diagram was generated,yielding 13 Wuling Powder⁃kidney stone intersected targets.A network of compound⁃target genes with 20 nodes and 19 interactions was constructed,in which,β⁃sitosterol was identified to be the most valuable compound.The PPI network found complex interactions among the proteins encoded by target genes.GO and KEGG enrichment analyses indicated that Wuling Powder could work by regulating G protein⁃coupled receptor signaling pathway,calcium signaling pathway,and calcium reabsorption mediated by other factors.The molecular docking was conducted on the most targeted gene CHRM3,showing thatβ⁃sitosterol could fit into the active pocket of CHRM3,thereby exerting potential therapeutic effects in kidney stone.Conclusion:G protein⁃coupled receptor signaling pathway,calcium signaling pathway,and calcium reabsorption mediated by other factors may be the potential molecular mechanism of Wuling Powder in the treatment of kidney stone.β⁃sitosterol may be a promising drug candidate for kidney stone.