Pedalitin could regulate lipid metabolism and attenuate inflammatory factors in a non-alcoholic fatty liver disease cell model

Nonalcoholic fatty liver disease (NAFLD) is an escalating global health issue, leading to liver fat accumulation, inflammation, fibrosis, and potential liver failure. In our preliminary network pharmacological study, it was hypothesized that Pedalitin (PED), a flavonoid found in black sesame plants, might exhibit protective effects against NAFLD. However, the effects and mechanisms of PED underlying its action on NAFLD are not yet fully understood. This study aimed to explore the potential effects and mechanisms of PED on NAFLD using a combination of network pharmacology, molecular docking, and the LO2 cell model. Potential targets for PED and NAFLD were predicted through public databases. Protein-protein interaction (PPI) networks were constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Molecular docking was used to predict the target genes that could bind to PED. In vitro experiments using the LO2 cell model indicated that PED significantly reduced TG level (p ​< ​0.05) and the formation of lipid droplets. The expression levels of key factors in fatty acid metabolism (CPT2, HADH), inflammatory factors (IL-17, TNF-α), and the FOXO signaling pathway (EGFR, IRS1, AKT1, FOXO1) were significantly downregulated in LO2 cells treated with PED (p ​< ​0.05). In conclusion, PED may modulate local lipid metabolism and mitigate inflammatory responses through the FOXO signaling pathway.