基于网络药理学和分子对接探讨小承气汤治疗慢性肾脏病的有效成分和作用机制

Effective Components and Mechanism of Xiaochengqi Decoction in the Treatment of Chronic Kidney Disease Based on Network Pharmacology and Molecular Docking

目的基于网络药理学和分子对接探讨小承气汤治疗慢性肾脏病的有效成分和作用机制。方法Herb数据库挖掘小承气汤的药物组分,Swiss ADME筛选潜在活性成分,Swiss Target Predidtion得到药物靶点基因,利用Cytoscape 3.9.0软件绘制“药物-活性成分-靶点”网络图以筛选核心成分。DrugBank数据库找到慢性肾脏病的靶点基因,运用Venny2.1.0作“药物-疾病”靶点图,String数据库得到PPI网络,Cytoscape3.9.0软件对该网络进行可视化处理以筛选核心靶点。DAVID数据库进行KEGG通路富集分析、GO功能分析,预测其可能的作用机制。最后,通过分子对接验证受体和配体的结合活性及位点。结果筛选活性成分大黄57种、枳实48种、厚朴62种,药物靶点共704个,慢性肾脏病靶点基因1074个,药物与疾病交集靶点169个。PPI提示AKT1、TNF、VEGFA、MAPK3、HIF1A、STAT3、CTNNB1、EGFR、PPARG、CASP3等靶点可能与小承气汤治疗慢性肾脏病有关。KEGG分析显示,脂质与动脉粥样硬化、PI3-Akt信号通路、NF-κB信号通路等可能参与了小承气汤治疗慢性肾脏病的过程。核心成分为magnolignan a,magnosalicin,3,4,5-trihydroxybenzoic acid。分子对接证明了核心靶点与核心成分之间存在较好的对接活性。结论通过网络药理学发现小承气汤治疗慢性肾脏病具有多成分、多靶点、多通路的特点,为小承气汤治疗慢性肾脏病提供了理论基础。

Objective To explore the effective components and mechanism of Xiaochengqi decoction in the treatment of chronic kidney disease based on network pharmacology and molecular docking.Methods Herb database was used to mine the drug components of Xiaochengqi decoction,Swiss ADME was used to screen potential active ingredients,Swiss Target Predidtion was used to obtain drug target genes,and Cytoscape 3.9.0 software was used to draw a"drug-active ingredient-target"network diagram to screen core components.DrugBank database was used to find the target genes of chronic kidney disease,Venny2.1.0 was used as the"drug-disease"target map,String database was used to obtain the PPI network,and Cytoscape3.9.0 software was used to visualize the network to screen the core targets.DAVID database was used for KEGG pathway enrichment analysis and GO function analysis to predict its possible mechanism of action.Finally,the binding activity and site of receptor and ligand were verified by molecular docking.Results Screening 57 kinds of active ingredients of rhubarb,48 kinds of Fructus Aurantii Immaturus,62 kinds of Magnolia officinalis,a total of 704 drug targets,1074 target genes of chronic kidney disease,169 targets of drug and disease intersection.PPI suggested that AKT1,TNF,VEGFA,MAPK3,HIF1 A,STAT3,CTNNB1,EGFR,PPARG,CASP3 and other targets might be related to the treatment of chronic kidney disease with Xiaochengqi decoction.KEGG analysis showed that lipid and atherosclerosis,PI3-Akt signaling pathway,NF-κB signaling pathway may be involved in the process of Xiaochengqi decoction in the treatment of chronic kidney disease.The core components were magnolignan a,magnosalicin,3,4,5-trihydroxybenzoic acid.Molecular docking proved that there was a good docking activity between the core target and the core component.Conclusion Xiaochengqi decoction has the characteristics of multi-component,multi-target and multi-pathway in the treatment of chronic kidney disease,which provides a theoretical basis for Xiaochengqi decoction in the treatment of chronic kidney disease.