Apigenin inhibits ethanol-induced oxidative stress and LPS-induced inflammatory cytokine production in cultured rat hepatocytes

Abstract

Apigenin is a natural flavonoid compound that has antioxidative, anti-inflammatory, and hepatoprotective effects, but the underlying mechanisms are still unclear. In this study, the effects of apigenin on ethanol-induced oxidative stress and lipopolysaccharide (LPS)-induced inflammatory cytokine production were examined in cultured rat hepatocytes. Following pretreatment of ethanol-stimulated hepatocytes with apigenin 6–24mM for 2h, the levels of cytochrome P450 2E1 (CYP2E1) protein expression and supernatant alanine aminotransferase and malondialdehyde were reduced (P<0.05 or P<0.01), while the activities of glutathione reductase and glutathione peroxidase were increased (P<0.05 or P<0.01). Likewise, the pretreatment of LPS-stimulated hepatocytes with the same concentrations of apigenin could decrease the levels of nuclear factor-κB protein expression and supernatant tumor necrosis factor-α and interleukin-6 (P<0.05 or P<0.01), and increase the level of IκB-α protein expression (P<0.05 or P<0.01). In all of these results, the concentration of 24μM was the most effective. These findings demonstrate that apigenin may exert an inhibitory effect on ethanol-induced oxidative stress and LPS-induced inflammation in the cultured hepatocytes, and its mechanisms may be related to the reduction of CYP2E1 expression, increment of antioxidative ability, and regulation of inflammatory gene expression.