Pacific Oyster-Derived Alcohol Dehydrogenase Activating Peptide Leu-Gln-Pro-Pro-Arg Ameliorates Alcoholic Liver Disease by Enhancing Alcohol Metabolism and Suppressing Mitochondrial-Mediated Apoptosis

Alcohol dehydrogenase (ADH) plays an important role in improving alcohol metabolism. Bioactive peptides, as functional factors with low toxicity and easy absorption, have attracted increasing attention in the intervention of alcoholic liver disease (ALD). This study investigated the effects of LQPPR, an ADH-activating peptide from Pacific oysters, on ALD and further elucidated its mechanism. The results indicated that LQPPR can reduce serum transaminase levels, ameliorate alcohol-induced liver histopathological changes, and exert a notable protective effect against ALD. From the perspective of alcohol metabolism, LQPPR enhanced ADH and ALDH activity while reducing CYP2E1 expression levels, thereby decreasing ROS and MDA content, improving SOD and GSH levels, and mitigating oxidative damage to hepatocyte mitochondria. Furthermore, LQPPR improved mitochondrial function by reducing oxidative damage, subsequently alleviating alcohol-induced disruptions in ATP and NADH/NAD+ levels. This downregulated the expression of Bax, cytochrome c, and cleaved caspase-3 in the liver, ultimately inhibiting the mitochondrial-mediated apoptosis pathway and exerting hepatoprotective effects. In summary, the ADH-activating peptide LQPPR can reduce hepatic oxidative damage by modulating alcohol metabolism, thereby preventing mitochondrial dysfunction and suppressing the mitochondrial-mediated apoptosis pathway. These results suggest that LQPPR may serve as a potential functional component for the prevention of ALD.