Preparation, identification, and functional properties of ADH-activating and hepatoprotective potential egg white peptides

Alcoholic liver disease (ALD) is a global health concern caused by chronic excessive alcohol consumption, and dietary intervention is a key strategy for improving ALD. This study aimed to develop egg white peptides (EWP) with enhanced alcohol metabolism functionality. By optimizing the stepwise enzymatic hydrolysis process, we successfully achieved activation rates of alcohol dehydrogenase (ADH) and ABTS free radical scavenging capacity in EWP of 35.76% and 43.12%, respectively. EWP showed adequate stability during processing and in vitro digestion. LC-MS/MS analysis identified 8,220 peptides. Computer-aided analysis screened four novel ADH-activating peptides (LAPGW, WLF, WPPP, and WFLPR). Molecular docking analysis confirmed that these peptides exhibit strong and stable binding to ADH through hydrophobic interactions, hydrogen bonds, and van der Waals forces. In an alcohol-damaged HepG2 cell model, these peptides significantly reduced levels of cellular damage markers (transaminases) by more than 29%. Mechanistic studies indicated these peptides exerted protective effects against alcoholic hepatocyte injury by accelerating alcohol metabolism and potentially modulating antioxidant enzyme activities—such as glutathione synthesis and superoxide dismutase—to synergistically alleviate oxidative stress. Graphical