基于网络药理学探讨金钱草治疗肾结石的作用机制

Mechanism of Herba Lysimachiae on Renal Calculi Based on Network Pharmacology

目的基于网络药理学探讨金钱草治疗肾结石的可能分子机制。方法基于TCMSP、SwissTargetPrediction数据库及Uniprot数据库筛选出金钱草的有效成分及靶点基因,通过GeneCards数据库及OMIM数据库筛选出肾结石的疾病靶点基因,用Cytoscape软件构建"药物-活性成分-疾病-靶点"相互作用网络图,将有效成分靶标与疾病靶标上传到String数据库,构建蛋白互作用网络图(PPI),并计算其特征值,使用R语言对得到的PPI进行核心基因的筛选,运用R语言对关键靶点进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果共筛选得到金钱草10个活性成分,涉及82个作用靶点;网络分析显示,靶点主要涉及NF-κappB结合、热休克蛋白结合、核受体活性、转录因子活性,直接的配体调节序列特异性DNA结合、类固醇结合、组蛋白激酶活性等生物学过程;富集分析显示,相关基因主要通过调节前列腺癌、Apoptosis、MAPK、p5等信号通路来发挥治疗肾结石的作用。结论金钱草中的槲皮素、山柰酚、金合欢素可能是其治疗肾结石的物质基础,其作用机制涉及了NF-κappB结合、热休克蛋白结合、核受体活性、转录因子活性,直接的配体调节序列特异性DNA结合、类固醇结合、组蛋白激酶活性等。

Objective To explore the possible molecular mechanism of Lysimachia in the treatment of renal calculi based on network pharmacology.Methods The effective components and target genes of Herba Lysimachiae were screened based on TCMSP,SwissTargetPrediction database and Uniprot database.The disease target genes of kidney stones were screened by GeneCards database and OMIM database.The"drug-active components-disease-target"interaction network diagram was constructed by Cytoscape software.The effective components and disease targets were uploaded to the String database.The protein interaction network diagram(PPI)was constructed and the eigenvalues were calculated.R language was used to screen the core genes of PPI,and R language was used to perform gene ontology(GO)enrichment analysis of key targets and Kyoto gene and genome encyclopedia(KEGG)pathway enrichment analysis.Results Ten active components of Lysimachia christinae were screened,involving 82 action targets.Network analysis showed that the target mainly involved in NF-κappB binding,heat shock protein binding,nuclear receptor activity,transcription factor activity,direct ligand regulatory sequence specific DNA binding,steroid binding,histone kinase activity and other biological processes;enrichment analysis showed that related genes mainly played a role in the treatment of renal calculi by regulating prostate cancer,apoptosis,MAPK,p5 and other signaling pathways.Conclusion Quercetin,kaempferol and acacia in S.mandshurica may be the material basis for its treatment of renal calculi.Its mechanism involves NF-κappB binding,heat shock protein binding,nuclear receptor activity,transcription factor activity,and direct ligand regulation of sequence-specific DNA binding,steroid binding,and histone kinase activity.