Protective Efficacy and Related Mechanism of a new ADH Activating Peptide YRPG from Lactococcus lactis Against Acute Alcohol-Induced Injury

Abstract

Excessive alcohol intake can cause severe acute alcohol injury (AAI). Alcohol dehydrogenase (ADH)-activating peptide is an effective means to alleviate this injury. This study investigated the protective effects of the ADH-activating peptide YRPG from Lactococcus lactis against AAI and further elucidated its underlying mechanism, while also assessing its stability. Results demonstrated that at a concentration of 10 mmol/L, YRPG achieved an in vitro ADH activation rate of 48.05% ± 1.11%. Notably, YRPG exhibited high gastrointestinal stability (81.61% ± 1.13%) and predominantly accumulated in liver. In an AAI mouse model, a single administration of YRPG before or after alcohol exposure significantly shortened intoxication duration, reduced blood alcohol concentration, enhanced ADH and acetaldehyde dehydrogenase activities, elevated antioxidant capacity, and alleviated gastric and liver injuries. Integrated metabolomic and network pharmacology analysis, validated by qRT-PCR and immunohistochemistry, revealed that the protective effect of YRPG against AAI may be related to the modulation of PI3K/AKT/FoxO3a pathway. This study confirmed the potential of YRPG in preventing and repairing AAI, providing a foundation for developing alcohol-detoxifying agents based on bioactive peptides.