Anti-atherosclerotic mechanisms of naringin based on network pharmacology and cellular experiments

LIU Yan; GAO Rong; TANG Xiaohan; MENG Yuting; WAN Zhiruo; GAO Cuiyun; YUAN Hailong

doi:10.3969/j.issn.2097-1753.2024.03.010

Abstract：Objective To explore the mechanism of action of naringin in the treatment of atherosclerosis based on network pharmacology and vitro cellular assays.Methods The PubChem platform and Pharmmapper online analysis platform were used to obtain targets of naringin,and Genecards,PharmGkb,TTD,Disgenet and Drugbank databases were searched for targets related to atherosclerosis diseases.The protein-protein interaction network was constructed to screen for the core targets while the main pathways and target proteins were screened via GO and KEGG enrichment analyses.Molecular docking was performed to determine the molecular basis of the interactions between naringin and the core targets.In vitro experiments were conducted with human umbilical vein endothelial cells(HUVEC)to verify the predicted results.Results A total of 220 potential targets of naringin were screened,5 253 targets were related to atherosclerosis,and 94 co-acting targets were identified.GO functional annotation resulted in a total of 281 entries,including 215 biological processes,25 cellular components,and 41 molecular functions.KEGG enrichment revealed a total of 36 pathways related to therapies for atherosclerosis.The molecular docking results demonstrated that naringin bound well to the five core targets.The results of cellular experiments showed that naringin could significantly reduce the migration and adhesion ability of HUVEC.Conclusion Naringin may inhabit atherosclerosis by regulating lipids,proteoglycan in cancer and MAPK signaling pathways through such key targets as the kinase insert domain receptor,recombinant plasminogen activator inhibitor 1 and tissue inhibitor of matrix metalloproteinase-1 which exert anti-atherosclerosis effects by regulating endothelial cell function,angiogenesis,cell proliferation and apoptosis.