Luteolin and luteolin-7-O-glucoside protect against acute liver injury through regulation of inflammatory mediators and antioxidative enzymes in GalN/LPS-induced hepatitic ICR mice

摘要

BACKGROUND/OBJECTIVES Anti-inflammatory and antioxidative activities of luteolin and luteolin-7- O -glucoside were compared in galactosamine (GalN)/lipopolysaccharide (LPS)-induced hepatitic ICR mice. MATERIALS/METHODS Male ICR mice (6 weeks old) were divided into 4 groups: normal control, GalN/LPS, luteolin, and luteolin-7- O -glucoside groups. The latter two groups were administered luteolin or luteolin-7- O -glucoside (50 mg/kg BW) daily by gavage for 3 weeks after which hepatitis was induced by intraperitoneal injection of GalN and LPS (1 g/kg BW and 10 μg/kg BW, respectively). RESULTS GalN/LPS produced acute hepatic injury by a sharp increase in serum AST, ALT, and TNF-α levels, increases that were ameliorated in the experimental groups. In addition, markedly increased expressions of cyclooxygenase (COX)-2 and its transcription factors, nuclear factor (NF)-κB and activator protein (AP)-1, were also significantly attenuated in the experimental groups. Compared to luteolin-7- O -glucoside, luteolin more potently ameliorated the levels of inflammatory mediators. Phase II enzymes levels and NF-E2 p45-related factor (Nrf)-2 activation that were decreased by GalN/LPS were increased by luteolin and luteolin-7- O -glucoside administration. In addition, compared to luteolin, luteolin-7- O -glucoside acted as a more potent inducer of changes in phase II enzymes. Liver histopathology results were consistent with the mediator and enzyme results. CONCLUSION Luteolin and luteolin-7- O -glucoside protect against GalN/LPS-induced hepatotoxicity through the regulation of inflammatory mediators and phase II enzymes.