Yizhou Fang, Lechen Zhang, Z D Yin, Jianhua Liu, Guangrong Huang
This study aimed to prepare and screen alcohol dehydrogenase (ADH)-activating peptides from sturgeon meat. Only myofibrillar protein had the potential to generate ADH-activating peptides through trypsin hydrolysis, and in vivo experiments demonstrated that the 1–3 kDa peptide fraction from the hydrolysate could prevent alcohol-induced liver injury by restoring ADH activity, enhancing antioxidant capacity, and reducing pro-inflammatory factors, with a preventive effect of 0.45 g/kg equivalent to 0.30 g/kg of metadoxine. Subsequently, two potential ADH-activating peptides, DIDIRKDLYANN and GVPADNVKDVIIW, were further screened via simulation-based prediction of molecular properties from the 1–3 kDa fraction. Synthetic validation not only confirmed the effectiveness of the screening but also revealed that the ADH activation ability of DIDIRKDLYANN even surpassed that of metadoxine at high concentrations, coupled with favorable solubility and non-allergenic properties. In conclusion, both the 1–3 kDa peptide fraction and DIDIRKDLYANN demonstrated significant industrial potential for development as anti-alcohol biopharmaceuticals or liver-protective functional foods.