基于网络药理学和分子对接探究丹参调节氧化应激的机制

Exploring The Mechanism of Salvia miltiorrhiza Regulating Oxidative Stress Based on Network Fharmacology and Molecular Docking

试验旨在基于网络药理学和分子对接技术,探讨丹参调节氧化应激的作用靶点与通路。通过TCMSP平台检索丹参的成分及蛋白靶点;经GeneCards和OMIM数据库获取氧化应激相关靶点;运用Cytoscape3.9.1软件及STRING数据库建立“丹参-活性成分-靶点”网络以及蛋白质-蛋白质相互作用(PPI)网络,对核心靶点进行筛选;由DAVID平台进行基因本体(GO)功能以及京都基因与基因组百科全书(KEGG)通路富集分析;依托AutoDockTools平台进行分子对接,对丹参活性成分与核心靶点的结合效能进行考察。筛选得到59个丹参调抗氧化的主要活性成分,主要有木犀草素、2-异丙基-8-甲基菲-3,4-二酮和二氢丹参内酯等,收集到肿瘤坏死因子(TNF)、白细胞介素-6(IL6)以及肿瘤蛋白p53(TP53)等关键作用靶点136个。GO和KEGG富集预测丹参主要依靠PI3K/AKT等信号通路干预氧化应激。分子对接结果显示,丹参活性成分与核心靶点具有较强的对接能力。研究基于网络药理学及分子对接探讨了丹参干预氧化应激的有效成分潜在的分子作用机制,为丹参保护畜禽免受氧化应激损伤提供了参考和思路。

The experiment is based on network pharmacology and molecular docking technology to explore the targets and pathways of Salvia miltiorrhiza in regulating oxidative stress.Components and protein targets of salvia miltiorrhiza were retrieved by TCMSP platform;the oxidative stress related targets were obtained by GeneCards and OMIM databases;the"Salvia miltiorrhiza-Active ingredient-target"network and protein-protein interaction(PPI)network were established by using Cytoscape3.9.1 software and STRING database to screen core targets.The gene ontology(GO)function and the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment were analyzed by the DAVID platform.Using AutoDockTools platform for molecular docking,the binding efficiency of active components of Salvia miltiorrhiza and core targets was investigated.59 major antioxidant active components of salvia miltior⁃rheum were screened,including luteolin,2-isopropyl-8-methylphenanthrene,4-dione and Dihydrotanshinlactone,and 136 key action targets such as tumor necrosis factor(TNF),interleukin-6(IL6)and tumor protein p53(TP53)were collected.GO and KEGG enrichment predicted that salvia miltior⁃rhiza mainly depended on PI3K/AKT signaling pathways to interfere with oxidative stress.Molecular docking results showed that active components of salvia miltiorrhiza had strong docking ability with core targets.Based on network pharmacology and molecular docking,this study explored the potential molecular mechanism of active components of Salvia miltiorrhiza to interfere with oxidative stress,and provided references and ideas for protecting livestock and poultry from oxidative stress damage.