摘要
Abstract
Objective:To analyze the potential mechanism of Salviae Miltiorrhizae Radix et Rhizoma in treating cyclosporine A(CsA)nephrotoxicity using network pharmacology combined with molecular docking technology.Methods:Active ingredients of Salviae Miltiorrhizae Radix et Rhizoma were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and their potential targets were predicted using TargetNet and SuperPred databases.The CsA nephrotoxicity-related disease targets were obtained from GenCLiP 3 and CTD databases.The Venny 2.1.0 tool was used to analyze the intersecting targets between the active ingredients of Salviae Miltiorrhizae Radix et Rhizoma and CsA nephrotoxicity.The STRING database was employed to construct a protein-protein interaction(PPI)network,which was visualized using Cytoscape software.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using the DAVID database.Molecular docking validation was conducted using AutoDock Vina software.Results:A total of 33 active ingredients and 373 potential targets of Salviae Miltiorrhizae Radix et Rhizoma were screened,along with 760 CsA nephrotoxicity-related disease targets,resulting in 100 intersecting targets.Among these,cryptotanshinone,tanshinone IIA,danshenol B,dihydrotanshinone I,baicalin,and α-amyrin were identified as the main active ingredients,while estrogen receptor 1(ESR1),hypoxia-inducible factor 1 alpha(HIF1A),heat shock protein 90 alpha family class A member 1(HSP90AA1),mechanistic target of rapamycin kinase(MTOR),nuclear factor kappa B subunit 1(NFKB1),prostaglandin-endoperoxide synthase 2(PTGS2),signal transducer and activator of transcription 1(STAT1),and signal transducer and activator of transcription 3(STAT3)were identified as core targets.The GO enrichment analysis yielded 141 entries,including 68 biological processes,30 cellular components,and 43 molecular functions.The KEGG enrichment analysis revealed 87 signaling pathways,primarily involving hypoxia-inducible factor-1(HIF-1),phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt),apoptosis,and Toll-like receptor signaling pathways.Molecular docking results demonstrated strong binding affinities between the main active ingredients of Salviae Miltiorrhizae Radix et Rhizoma and the core targets.Conclusion:Salviae Miltiorrhizae Radix et Rhizoma may alleviate CsA nephrotoxicity through an integrated mechanism involving multiple ingredients synergistically regulating multiple targets and pathways.关键词
环孢素A肾毒性/丹参/网络药理学/分子对接/作用机制Key words
Cyclosporine A nephrotoxicity/Salviae Miltiorrhizae Radix et Rhizoma/Network pharmacology/Molecular docking/Mechanism of action分类
医药卫生
