基于网络药理学和分子对接研究芪金合剂治疗肾结石的作用机制

Mechanism of Qijin Mixture in the Treatment of Kidney Stones Based on Network Pharmacology and Molecular Docking

目的利用网络药理学和分子对接技术预测芪金合剂(黄芪、金钱草)治疗肾结石的作用机制及潜在靶点。方法利用多个数据库获取药物有效成分、疾病靶点,取两者交集基因;使用Cytoscape 3.8.0软件构建“中药-成分-靶点”调控网络,将交集靶基因导入STRING数据库,构建蛋白质相互作用网络;并对交集基因进行拓扑分析、GO和KEGG富集分析;将有效成分与核心基因分子对接,计算最低结合能,制作分子对接模型图。结果获得黄芪有效成分21种,金钱草有效成分10种,黄芪作用靶点396个,金钱草作用靶点263个,交集基因109个;根据KEGG富集分析结果获得作用通路9条;“中药-成分-靶点”网络图中芪金合剂的有效成分为槲皮素、山柰酚、异鼠李素;槲皮素与核心基因分子对接结合稳定。结论芪金合剂可通过多靶点、多通路、多成分治疗肾结石,槲皮素、山柰酚、异鼠李素可能是其治疗作用的主要有效成分,其潜在的作用机制与炎症、氧化应激反应、代谢、激素及免疫等通路密切相关,其作用靶点可能与AKT1、MAPK1、MAPK14、TNF、ESR1、JUN、FOS、TP53、MYC等多个基因有关。

Objective The mechanism and potential targets of Qijin Mixture[Huangqi(Astragali Radix),Jinqiancao(Lysimachiae Herba)]in the treatment of kidney stones were predicted by network pharmacology and molecular docking technology.Methods Multiple databases were used to obtain drug active ingredients and disease targets,their intersection genes were selected;Cytoscape 3.8.0 software was used to construct a“traditional Chinese medicine-component-target”regulatory network,and the intersection target genes were imported into the STRING database to construct a protein-protein interaction network;and topological analysis,GO and KEGG enrichment analysis were performed for the intersection genes;the active ingredients and the core gene molecules were docked,the lowest binding energy was calculated,and a molecular docking model diagram was made.Results 21 kinds of active ingredients of Huangqi(Astragali Radix)were obtained,10 kinds of active ingredients of Jinqiancao(Lysimachiae Herba)were obtained,396 targets of Huangqi(Astragali Radix)were obtained,263 targets of Jinqiancao(Lysimachiae Herba)were obtained,and 109 intersection genes were obtained.According to the results of KEGG enrichment analysis,9 action pathways were obtained;the effective ingredients of Qijin Mixture in the network diagram of“traditional Chinese medicine-component-target”were quercetin,kaempferol and isorhamnetin;quercetin was stable in docking and binding with core gene molecules.Conclusion Qijin Mixture can treat kidney stones through multiple targets,multiple pathways,and multiple components.Quercetin,kaempferol and isorhamnetin may be the main active components of its therapeutic effect,and its potential mechanism of action is closely related to inflammation,oxidative stress response,metabolism,hormone and immune pathways,and its targets may be related to multiple genes such as AKT1,MAPK1,MAPK14,TNF,ESR1,JUN,FOS,TP53,MYC.