The Mechanism of Berberine-TanshinoneⅡA for the Treatment of Atherosclerosis Based on Network Pharmacology and Molecular Docking Technology
Objective:To investigate the potential targets and pathways of "berberine-tanshinone ⅡA" against atherosclerosis by network pharmacology and molecular docking methods. Methods:The molecular structure and targets of berberine-tanshinone ⅡA were obtained from PubChem database,and the targets were predicted by SwissTargetPrediction platform.The therapeutic targets of atherosclerosis were searched and screened through GeneCards,OMIM and DisGeNET databases,and the intersection of drug targets and disease targets was obtained.The protein-protein interaction(PPI) network was constructed by STRING 11.5 database,and the topology was analyzed by Cytoscape 3. 9. 1 software. The gene ontology ( GO) function enrichment analysis and the Kyoto Encyclopedia of Genomes(KEGG) pathway enrichment analysis were performed for the intersection targets through DAVID database. AutoDock Tools 1.5.6 and PyMOL 2.5.5 were used for molecular docking study.Results:A total of 95 intersection targets of berberine-tanshinone ⅡA-atherosclerosis were obtained.The core targets of protein interaction analysis to explore the possible action of active components mainly included proto-oncogene tyrosine protein kinase(SRC),phosphatidylinositol-3-kinase regulatory subunit 1(PIK3R1),phosphatidylinositol-4,and phosphatidylinositol-4,5-diphosphate 3-kinase catalytic subunit α(PIK3CA),cell division cyclin 42(CDC42),lymphocyte specific protein tyrosine kinase(LCK),Janus kinase 2(JAK2),Abelson murine leukemia virus oncogene homology 1(ABL1),and RAS-associated C3 botulinum toxin substrate 1(RAC1).The results of GO functional enrichment analysis showed that the anti-atherosclerosis of berberine-tanshinone Ⅱ A mainly involved 230 biological functions,such as protein phosphorylation,signal transduction,response to exogenous stimuli,response to drugs,and immune response. Enrichment results of KEGG signal pathway involved 106 signaling pathways,such as the potential pathways of berberine-tanshinositone ⅡA against atherosclerosis included lipid and atherosclerosis signaling pathway,neurotrophin signaling pathway,phosphatidylinositol 3-kinase ( PI3K)/protein kinase B ( AKT) signaling pathway,vascular endothelial growth factor ( VEGF) signaling pathway,mitogen-activated protein kinase ( MAPK) signaling pathway,mouse sarcoma ( Ras) signaling pathway. The binding energies of berberine-tanshinone ⅡA were all<-20. 92 kJ/mol,indicating that the key targets and berberine-tanshinone ⅡA had better binding activity. The highest binding energy of berberine-tanshinone ⅡA was the target protein SRC,which showed strong binding activity between them.Conclusion:Berberine-tanshinone ⅡA might play anti-atherosclerosis effects on multiple signaling pathways such as lipid,PI3K/AKT,VEGF,MAPK and Ras through multiple targets such as SRC,PIK3R1,PIK3CA and CDC42. Molecular docking results showed that berberine-tanshinone ⅡA showed better binding activity with the predicted core targets,which provided an application for further study.
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维普
