基于网络药理学及分子对接研究三七总皂苷治疗肾纤维化的作用机制

目的:本研究利用网络药理学及分子对接技术预测三七总皂苷入血成分的抗纤维化作用机制,探讨其药效物质基础及作用途径。方法:检测并确定三七总皂苷的主要入血成分为潜在活性成分,采用PharmMapper系统,结合CooLGeN及GeneCards服务器筛选成分的潜在靶点;通过DAVID平台进行基因本体（GO）功能富集分析和京都基因和基因组百科全书（KEGG）通路富集分析;采用STRING数据库和Cytoscape软件绘制蛋白质-蛋白质相互作用(PPI)网络及“入血成分-靶点-通路-疾病”网络;使用Autodock Vina软件对入血成分与潜在关键靶点进行分子对接。结果:确认三七总皂苷入血成分20个,得到入血成分治疗肾纤维化的潜在靶点31个,涉及细胞内信号转导、凋亡、增殖、基质分解等生物过程和PI3K-AKT、Rap1、HIF-1、FoxO等8个显著相关信号通路。网络分析表明,AKT1、SRC、CASP3、NOS2、EGFR等是抗肾纤维化的关键靶点。分子对接结果显示,入血成分人参皂苷Rh2、丙二酰人参皂苷Rb1、人参皂苷Rb1、人参皂苷Rg2、人参皂苷Rb3、人参皂苷Rb2、人参皂苷Rg3等与主要靶点AKT1、SRC、CASP3、NOS2的结合活性较强。结论:初步揭示三七总皂苷治疗肾纤维化多成分、多靶点、多通路的作用机制,为后续的药理研究及临床开发提供新思路和科学依据。

Mechanism of Panax Notoginseng Saponins Against Renal Fibrosis Based on Network Pharmacology and Molecular Docking

To predict the anti-fibrosis mechanism of absorbed components of Panax notoginseng saponins(PNS),and to explore its effective substances and action pathways by network pharmacology and molecular docking.Methods:Absorbed components of PNS were detected and determined as potential active components,and their potential action targets were screened by PharmMapper combined with CooLGeN and GeneCards.Gene Ontology(GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were carried out through DAVID.Protein-protein interaction(PPI) network and absorbed component-target-pathway-disease network were plotted using STRING and Cytoscape.Molecular docking between absorbed components and potential key targets were conducted by Autodock Vina.Results:Twenty absorbed components of PNS were determined,and 31 potential targets for the treatment of renal fibrosis were obtained,involving biological processes such as intracellular signal transduction,apoptosis,proliferation,matrix decomposition and hypoxia response,as well as eight significantly related signal pathways such as phosphoinositide-3-kinase/protein kinase B(PI3K/Akt),Ras-associated protein 1(Rap1),hypoxia-inducible factor-1(HIF-1) and forkhead box O(FOXO) signal pathways.Network analysis showed that AKT1,SRC,CASP3,NOS2 and EGFR were the key targets of anti-renal fibrosis.Molecular docking indicated that ginsenoside Rh2,malonyl ginsenoside Rb1,ginsenoside Rb1,ginsenoside Rg2,ginsenoside Rb3,ginsenoside Rb2 and ginsenoside Rg3 had strong binding activity to AKT1,SRC,CASP3 and NOS2.Conclusion:This study preliminarily revealed the multi-component,multi-target and multi-channel mechanism of PNS in the treatment of renal fibrosis,which provided new ideas and scientific basis for subsequent in-depth pharmacological research and clinical development.