Salvianolic acid A alleviates chronic ethanol-induced liver injury via promotion of β-catenin nuclear accumulation by restoring SIRT1 in rats.

In recent years, alcoholic liver disease (ALD) has emerged as a growing public health problem worldwide. β-catenin plays an important role in the growth, development, regeneration and metabolic activity of the liver. Salvianolic acid A (SalA) is a water-soluble component from the root extract of Salvia miltiorrhiza Bunge, and its effect on ALD has not yet been investigated. This study aimed to investigate the effect of SalA on chronic alcohol-induced liver injury and to explore the role of SIRT1-mediated β-catenin deacetylation in such an effect. In this study, SalA treatment significantly alleviated the accumulation of lipid droplets and reduced the plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), alcohol and ammonia levels in rats. SalA enhanced ethanol and ammonia metabolism and maintained mitochondrial homeostasis. Moreover, SalA restored the activity of the major ethanol-metabolizing enzymes and oxidative stress functions in the liver. Importantly, we found that SalA treatment effectively inhibited the ethanol-mediated decrease in nuclear β-catenin by upregulating SIRT1 in the liver. SIRT1 then deacetylated β-catenin to promote its accumulation in the nucleus, thereby preventing alcohol-induced liver injury. The results demonstrate that the SIRT1/β-catenin pathway is a key therapeutic target in liver injury caused by chronic alcohol exposure and that SalA protects against alcohol-induced liver injury via the SIRT1-mediated deacetylation of β-catenin.