Glutathione-rich yeast extract improves alcohol-associated liver diseases through the improvement of mitochondrial dysfunction and oxidative stress by activating SIRT3

Alcohol-associated liver diseases (ALD) is a chronic liver disease characterized by mitochondrial dysfunction and oxidative stress. Glutathione (GSH)-rich yeast extract (GYE) is a product abundant in proteins, amino acids, fiber, trace elements, and GSH. Previous studies have reported that GYE exhibits anti-inflammatory and antioxidant properties. However, the effect of GYE on ALD and its underlying mechanisms remain largely unclear. In the present study, we investigated whether GYE could protect against ALD using ethanol-treated mice and HepG2 cells, with a specific focus on mechanisms involving the amelioration of ethanol-induced mitochondrial damage and oxidative stress. The results showed that GYE significantly ameliorated liver injury in chronic ethanol-feeding mice. In addition, GYE increased the content of GSH in the liver, thereby protecting against ethanol-induced oxidative stress and mitochondrial dysfunction. Moreover, the expression of SIRT3 was measured to reveal potential targets by which GYE protected against ALD. Our results showed that the ethanol-induced inhibition of SIRT3 expression was reversed by GYE in vivo and in vitro. Silencing of SIRT3 by siRNA markedly weakened the protective effect of GYE on mitochondrial function and oxidative stress. Our findings suggest that GYE alleviates ethanol-induced mitochondrial damage and oxidative stress via activating SIRT3 in an ALD mouse model, which highlights a promising prevention strategy for ALD. • GYE significantly ameliorated ALD in chronic ethanol-feeding mice. • GYE protected against ethanol-induced oxidative stress and mitochondrial dysfunction. • GYE inhibited oxidative stress and improved mitochondrial function by activating SIRT3.