Evaluation of Metabolic Dysfunction-Associated Fatty Liver Disease-Related Pathogenic Mechanisms in Human Steatotic Liver Cell-Based Model: Beneficial Effects of Prunus domestica L. subsp. syriaca Extract

Background/Objectives: Disrupted glucose uptake, oxidative stress, and increased de novo lipogenesis are some of the key features of metabolic dysfunctionassociated fatty liver disease (MASLD). The modulation of these pathogenic mechanisms using extracts from natural and sustainable sources is a promising strategy to mitigate disease progression. This study aimed to evaluate the effects of Prunus domestica L. subsp. syriaca extract on these processes, taking advantage of a cell-based model of steatotic hepatocytes (HepG2-OA) that recapitulates some key pathophysiological features of MASLD. Methods: The HepG2-OA cell model was generated by treating cells for 7 days with 100 μM oleic acid (OA). The effect of different concentrations (0.01, 0.1, 0.5, and 1 mg/mL) of P. domestica extract was assessed through MTT assay (cell viability), flow cytometry (glucose uptake and reactive oxygen species, ROS, production), spectrophotometry (lipid accumulation), and qRT-PCR (expression of selected genes). Results: P. domestica extract exhibited no cytotoxicity at any tested concentration after 24 and 48 h in the HepG2-OA cells. The extract increased glucose uptake in a dose-dependent fashion after both 6 and 24 h. Additionally, the extract reduced lipid accumulation and downregulated the expression of key lipogenic genes (DGAT1 and FASN). Furthermore, in the HepG2-OA cells, P. domestica extract reduced ROS production and downregulated the expression of oxidative stressrelated genes (SOD and CAT). Conclusions: P. domestica extract positively modulated some key molecular mechanisms associated with glucose metabolism, lipogenesis, and oxidative stress, supporting its potential as a nutraceutical candidate for MASLD management.