Luteolin protects against alcoholic liver injury by restoring NRF2 stability to suppress ACSS2 nuclear accumulation.

Alcohol abuse results in alcoholic liver disease which are associated with high morbidity and mortality worldwide. Whereas luteolin has shown potential hepatoprotective effects on ethanol-induced liver damage and the underlying mechanism remains unclear. In this study, a chronic plus a single binge ethanol feeding mouse model was employed to mimic acute-on-chronic alcoholic liver injury in humans, and the primary hepatocytes were isolated for the mechanism investigation. Our study demonstrated that luteolin protects against ethanol-induced liver injury by restoring NRF2 stability, thereby blocking the nuclear accumulation of ACSS2 and histone H3 acetylation. This subsequently led to reduced hepatic lipogenesis, and ultimately ameliorated alcoholic liver damage. Our findings elucidate the protective mechanism of luteolin in alcoholic liver injury and provide a new therapeutic strategy for the treatment of alcoholic liver disease.