Naringin and hepatic metabolic dysfunction in diabetes and metabolic syndrome: mechanisms and therapeutic perspectives.
Hepatic metabolic dysfunction is a central feature of diabetes mellitus and metabolic syndrome and plays a major role in the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). This review aims to summarize and critically analyze the effects of naringin (NAR), a citrus-derived flavonoid, on hepatic metabolic dysfunction associated with metabolic disorders, with particular emphasis on underlying molecular mechanisms and translational relevance. Experimental and clinical evidence indicates that NAR exerts hepatoprotective effects through the modulation of multiple interconnected pathways involved in metabolic injury, including oxidative stress, inflammatory signaling, lipid homeostasis, mitochondrial function, and autophagy. These effects are mediated, at least in part, through AMPK-, PPARα-, and NF-κB- related signaling pathways. Despite the consistent beneficial effects observed in preclinical models, significant discrepancies remain between experimental efficacy and clinically achievable concentrations, highlighting important pharmacokinetic and pharmacodynamic limitations. Emerging strategies aimed at improving bioavailability and therapeutic targeting may help bridge this translational gap. In conclusion, current evidence supports NAR as a promising multitarget therapeutic candidate for hepatic metabolic dysfunction; however, further studies addressing pharmacological optimization and clinical translation are required to fully establish its therapeutic potential.