Exploring the molecular mechanism of naringin dihydrochalcone intervention in atherosclerosis based on network pharmacology,molecular docking and cell experiments
Objective:To explore the target and molecular mechanism of naringin dihydrochalcone in the treatment of atherosclerosis using network pharmacology,molecular docking techniques and cell experiments.Methods:The potential targets of AS and naringin di-hydrochalcone were obtained through databases such as GeneCards,TTD,OMIM,and Swiss Target Prediction.A Venn diagram was uti-lized to identify the common targets of the two compounds.Subsequently,these targets were imported into the STRING online platform to construct a protein-protein interaction(PPI)network diagram.The core intersecting target map was generated using Cytoscape 3.8.2 software.Additionally,the core targets were inputted into the DAVID database for Gene Ontology(GO)and KEGG pathway enrichment analysis.Molecular docking validation of the drug and core targets was performed using AutoDock 4.2.6 software.Finally,human umbili-cal vein endothelial cells were selected to establish an oxidative stress cell model induced by H2O2 for in vitro biological validation of AS.Results:Through retrieval,2 044 disease targets related to AS and 100 action targets of naringin dihydrochalcone were obtained.The Venn diagram screening yielded 38 intersection targets.The PPI network analysis identified 10 core targets,ranked by MCC score as follows:EGFR,CASP3,ESR1,MTOR,FN1,MMP9,PARP1,PIK3CA,CTSD,and CDK2.The analyses of GO and KEGG pathways indicated that these targets were mainly involved in inflammation,the PI3K/Akt signaling pathway,and the signaling pathways of pro-grammed cell death,etc.The results of molecular docking analysis demonstrated that naringin dihydrochalcone had favorable binding efficacy with multiple core targets.Cell experiments revealed that compared with the Control group,the expression levels of reactive oxy-gen species(ROS)and Cleaved caspase-3 in the H2O2 group increased(F=17.77,73.31,both P<0.001),and the expressions of NF-κB p65,MMP-9,and TNF-α proteins were significantly upregulated(F=22.65,18.64,9.97,all P<0.05).Compared with the H2O2 group,high concentrations of naringin dihydrochalcone could inhibit the intracellular ROS(P<0.01)and the increased expression of Cleaved caspase-3(P<0.001),inhibit the activation of NF-κB p65(P<0.01),and downregulate the expressions of MMP-9 and TNF-α proteins(P<0.01).Conclusion:Naringin dihydrochalcone can play a role in the treatment of AS through multiple targets and multiple pathways.
万方数据
维普
