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

Nutr Res Pract. 2019 Dec;13(6):473-479. doi: 10.4162/nrp.2019.13.6.473. Epub 2019 Sep 9.

Abstract

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.

Keywords: Inflammation; Luteolin; Luteolin-7-O-glucoside; NF-E2-Related Factor 2; NF-kappa B.