Dietary Polyphenols and Their Impact on Nrf2 Pathway in Non‐Alcoholic Fatty Liver Disease: A Review of In Vitro and In Vivo Studies

Oxidative stress is a critical event in the development of metabolic disorders, including non-alcoholic fatty liver disease (NAFLD), diabetes, and cardiovascular diseases. Recent research has increasingly focused on the potential benefits of dietary polyphenols in mitigating oxidative stress and its associated complications. A crucial player of the antioxidant defense system is nuclear factor erythroid 2-related factor (Nrf2), a pivotal redox-responsive transcription factor that acts as a cytoprotective element and key regulator of the intracellular antioxidant reactions against damages mediated by oxidative insults. This review summarizes the key pathophysiological events in the development of NAFLD including oxidative stress and collects the main findings of current in vitro/in vivo investigations on the impact of polyphenols in the antioxidant responses in NAFLD models and discusses the implications of this evidence for future directions. This review provides the evidence that polyphenols improve metabolic health status through direct and indirect regulation of the Keap1/Nrf2/ARE signaling pathway and its dependent intracellular molecular cascades. However, this review primarily focuses on preclinical studies and clinical evidence is limited. Despite extensive preclinical evidence indicating that polyphenols have significant antioxidant properties and may mitigate oxidative stress-related conditions, the translation of these findings into human studies remains limited due to insufficient clinical data and the need for more rigorous methodologies to assess their efficacy in diverse populations.