Biodata Mining-based Elucidation of Mechanisms of Hesperetin as a Candidate for Atherosclerosis

Abstract BackgroundHesperetin, an active ingredient derived from Citrus × aurantium L., possesses a wide range of biological activities, including anti-inflammatory, anti-oxidation, and anti-cancer activity. Notably, hesperetin has been proposed as a candidate for atherosclerosis owing to the lipid-regulating and anti-inflammatory effect, while the underlying mechanisms remains obscure.ResultsIn our present study, the pharmacological and molecular properties of hesperetin were first evaluated to determine the druggability of hesperetin. Subsequently, 53 hesperetin-atherosclerosis crossover targets were collected to establish the protein-protein interaction network. The result of Gene Ontology enrichment analysis indicated that the crossover targets were involved in the regulation of lipid metabolism and inflammatory response. Moreover, the Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated that the crossover targets were highly correlated with the pathogenesis of atherosclerosis, such as fluid shear stress and atherosclerosis pathway and the TNF signaling pathway. Finally, an entire hesperetin-target-pathway network was constructed to provide a systematic overview of the pharmacological mechanisms of action of hesperetin against atherosclerosis.ConclusionsThe pharmacological mechanisms of actions of hesperetin against atherosclerosis was unveiled based on biodata mining from the public database and the bioinformatics data analysis-based strategy in this study, contributing to a deeper understanding of the molecular mechanisms of hesperetin in the treatment of atherosclerosis. Based on the results of network pharmacology analysis, we can conclude that hesperetin is surely an excellent candidate for atherosclerosis. We believe our work would be beneficial for further research and development of hesperetin as a natural active ingredient derived from Citrus × aurantium L. for the treatment of atherosclerosis.