The mechanism of salvia miltiorrhiza in the treatment of idiopathic tinnitus based on network pharmacology and molecular docking
Objective:To study the mechanism of salvia miltiorrhiza in the treatment of idiopathic tinnitus through network pharmacolo-gy and molecular docking.Methods:The drug components of salvia miltiorrhiza were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the Swiss Target Prediction was used to predict the target of drug components.GeneCards and OMIM were used to obtain disease targets of idiopathic tinnitus,and venny 2.1 was used to obtain intersec-tion targets.Protein-protein interaction(PPI)network analysis was conducted using STRING,and network diagram was constructed with Cytoscape.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed using DAVID database.The Component-Target-Pathway network diagram was constructed using Cytoscape software.Molecular docking was performed using chemical databases(PubChem),biomacromolecule structure databases(PDB),molecular visualization software(PyMoL)and AutoDock Tools1.5.7 software.Results:It was found that 31 active components of Salvia miltiorrhiza directly acted on 13 disease targets to treat id-iopathic tinnitus through multiple pathways,among which lutein,digitalone,notemschenone and cryptotanshinone were core compo-nents,and PTPT11,TERT,STAT3,MMP9 and AKT1 were crucial targets.The results of gene function annotation analysis showed that the biological processes most likely related to intersection genes mainly involved cellular response to UV-A,negative regulation of intrin-sic apoptotic signaling pathway,cellular response to lipopolysaccharide,negative regulation of apoptotic process,etc.Cell components mai-nly involved extracellular space,extracellular exosome,extracellular matrix,nucleoplasm,plasma membrane,etc.The molecular functions mainly involved serine-type endopeptidase activity,endopeptidase activity,peptidase activity,metalloendopeptidase activity,ATP binding and so on.The results of pathway enrichment analysis showed that salvia miltiorrhiza was mainly involved in lipid and ather-osclerosis,relaxin,adipocytokine,prolactin(PRL),interleukin(IL)-17,endocrine resistance,tumor necrosis factor(TNF),estrogen and other signaling pathways.Molecular docking analysis showed good binding force between lutein and the targets of MMP9,TERT,and AKT1.Conclusion:Salvia miltiorrhiza treats idiopathic tinnitus by regulating PTPT11,TERT,STAT3,MMP9,AKT1 and other targets of lipid and atherosclerosis,relaxin,adipocytokine,PRL,IL-17,endocrine resistance,TNF,estrogen and other signaling pathways.
salvia miltiorrhizaidiopathic tinnitusnetwork pharmacologymolecular dockingaction mechanism
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