A Phenolic Acid and Flavonoid Fraction Isolated from Lolium multiflorum Lam. Prevents d-Galactosamine-Induced Liver Damages through the Augmentation of Nrf2 Expression.

The aims of this study were to explore whether a phenolic acid and flavonoid fraction (named PAFF) isolated from Lolium multiflorum Lam. protects against d-galactosamine (GalN)-induced liver damages in mice and to investigate the associated mechanisms. ICR mice received oral administration with various concentrations (50, 100, and 200 mg/kg body weight) of PAFF once per 2 days for seven times before intraperitoneal injection with 800 mg/kg GalN. After a day of GalN challenge, blood and tissue samples were analyzed by biochemical, histopathological, real time RT-PCR, and Western blot methods. GalN challenge induced severe damage to hepatocytes with hepatocellular vacuolization and necrosis. GalN treatment increased serum ALT, ALP, AST, and LDH levels and hepatic MDA levels and stimulated mRNA and protein expressions of Nrf2 and HO-1 in the liver. GalN treatment also diminished the levels of GSH and the activities of CAT, SOD, and GPx in the liver. However, combined treatment with PAFF inhibited GalN-mediated increases in the histological damages and the levels of serum enzymes and hepatic MDA, restored the activities of hepatic antioxidant enzymes up to those in the control values, and augmented the GalN-stimulated expression of Nrf2 and HO-1 in the liver. Furthermore, PAFF treatment alone increased the cellular SOD activity and the expression of Nrf2 and HO-1 in the liver. Our results suggest that PAFF may protect against GalN-induced liver damage by decreasing oxidative stress and increasing cellular antioxidant activities through an activation of Nrf2/HO-1-dependent pathway.