Exploration of potential targets and mechanisms of naringenin in the treatment of nonalcoholic fatty liver disease through network pharmacology

Abstract

Objective: This study aimed to use network pharmacology to investigate the molecular mechanisms and potential targets of naringenin (NR) for nonalcoholic fatty liver disease (NAFLD) treatment to offer new drug development ideas. Methods: The structure and compound information of NR were obtained from PubChem and the traditional Chinese medicine system pharmacology database and analysis platform. The traditional Chinese medicine system pharmacology database and analysis platform Database, Comparative Toxicogenomics Database and Encyclopedia of Traditional Chinese Medicine Database were then used to predict the related targets of NR. Online mendelian inheritance in man, Disgenet, Gene cards, The therapeutic target database and Drug bank were used to screen NAFLD targets, and the intersection analysis was performed with the targets of NR active components to obtain the targets of NR in the treatment of NAFLD. The protein-protein interaction network of therapeutic targets was constructed by protein-protein interaction networks functional enrichment analysis 11.0, and gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis of therapeutic targets was performed by Metascape platform. Results: In this study, 171 NR targets and 1748 potential targets of NAFLD were screened, and 89 crossover targets and 16 core targets were screened and finally obtained. A total of 176 GO items were obtained by GO enrichment analysis (P < .05), including 389 biological process, 6 cell composition and 30 molecular function. A total of 137 signaling pathways were obtained by Kyoto encyclopedia of genes and genomes pathway enrichment and screening (P < .05). The core targets of NR in the treatment of NAFLD are TP53, CASP3, PRKCA, AKT1, RELA, PPARG, NCOA2, CYP1A1, ESR1, MAPK3, STAT3, JAK1, MAPK1, TNF, PPARA and PRKCB. Enrichment analysis showed that NR mainly involved in biological processes such as cellular response to nitrogen compound, regulation of miRNA transcription and negative regulation of miRNA-mediated gene silencing. It regulates Hepatitis B, Lipid and atherosclerosis, cytomegalovirus infection, Hepatitis C, AGE-RAGE signaling pathway in diabetic patients complications and other ways play a role in the treatment of NAFLD. Conclusions: The therapeutic effect of NR on NAFLD has the characteristics of multi-targets and multi-pathways, which provides a preliminary theoretical basis for clinical trials and the development of new drugs.