Selenium‐Containing Tea‐Derived Peptides Activate Alcohol Dehydrogenase and Ameliorate Alcohol‐Induced Liver Injury by Modulating Oxidative Stress Homeostasis

ABSTRACT Excessive alcohol consumption disrupts the hepatic redox homeostasis, inhibiting the alcohol dehydrogenase activity (ADH), resulting in ethanol metabolic disorders and oxidative liver injury. Selenium‐containing tea‐derived peptides (TSE‐PP) represent promising natural bioactive components combining enzymatic activation with antioxidant protection. This study established a preparation strategy oriented by ADH activation rate. After optimization by response surface methodology (RSM), the protein content of the resulting product was 67.38 ± 1.23%, with a selenium content of 1.07 ± 0.08 mg/kg and an ADH activation rate of 61.52 ± 2.11%. LC‐MS/MS identified 319 peptides, including 26 selenium‐modified sequences. Enzyme kinetic analysis showed that TSE‐PP could increase the Michaelis constant (Km) and the maximal velocity (Vmax) for ADH, indicating enhanced enzyme‐substrate affinity and catalytic efficiency. In an acute alcohol‐induced liver injury mouse model, TSE‐PP intervention significantly reduced intoxication duration, enhanced hepatic ADH activity, and effectively alleviated hepatocyte damage. TSE‐PP enhanced the activity of the superoxide dismutase–glutathione–glutathione peroxidase (SOD–GSH–GPx) antioxidant axis and reduced the content of lipid peroxidation product malondialdehyde (MDA), systematically reshaping the hepatic redox homeostasis. These findings provide a theoretical basis for the development of TSE‐PP as a functional ingredient in hangover relief and liver protection products.