Dietary Polyphenols from Dendropanax morbifera Leaves Ameliorate Alcohol-Induced Liver Injury Through Regulation of Oxidative Stress and Nrf2 Signaling.

Background/Objectives: Excessive alcohol consumption induces hepatic injury primarily through cytochrome P450 2E1 (CYP2E1)-mediated reactive oxygen species (ROS) generation and disruption of redox homeostasis. This study investigated the hepatoprotective effects of the ethyl acetate fraction from Dendropanax morbifera leaves (DMLEAF) against ethanol-induced oxidative damage in vitro and in vivo. Methods: The protective mechanisms of DMLEAF were evaluated in HepG2 cells exposed to ethanol (400 mM, 24 h) and in an acute ethanol-induced liver injury mouse model. Cellular ROS levels, apoptosis, antioxidant enzyme activities, and nuclear factor erythroid 2-related factor 2 (Nrf2) translocation were assessed in vitro. Serum biochemical markers, histopathological changes, and hepatic CYP2E1 mRNA expression were analyzed in vivo. Results: In HepG2 cells, DMLEAF significantly reduced intracellular ROS levels and apoptosis, improving cell viability by up to 27.2% and reducing apoptosis by approximately 32%. DMLEAF also attenuated the ethanol-induced decrease in antioxidant enzyme activities (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and promoted nuclear translocation of Nrf2. In mice, oral administration of DMLEAF significantly reduced serum alanine aminotransferase and aspartate aminotransferase levels, improved histopathological alterations, and suppressed hepatic CYP2E1 mRNA expression by 2.6-fold compared with ethanol-treated controls, while preventing the reduction in hepatic antioxidant enzyme activities. Conclusions: These findings suggest that DMLEAF mitigates alcohol-induced liver injury through suppression of CYP2E1-associated ROS production and activation of Nrf2-mediated antioxidant defense mechanisms.