Apigenin has a protective effect on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced mouse liver injury through the increments of hepatic nuclear factor erythroid 2-related factor 2 (Nrf-2) and peroxisome proliferator-activated receptor γ (PPARγ) expressions, but its exact mechanisms are still uncertain. This study aimed to further verify its protective effect on hepatocytes and to determine its target of action. The results showed that after treatment of D-GalN/LPS-stimulated hepatocytes with 2.5-20 μM apigenin, the supernatant alanine aminotransferase, aspartate aminotransferasein, tumor necrosis factor-α, and malondialdehyde levels and intracellular nuclear factor-κB protein expression were decreased, while the supernatant superoxide dismutase (SOD) and catalase (CAT) levels, intracellular PPARγ and inhibitor of kappa B-alpha protein expressions, and nucleus Nrf-2 protein expression were increased. After pretreatment with BML-111 or GW9662, the apigenin-induced nucleus Nrf-2 or intracellular PPARγ protein expressions were completely inhibited, respectively, but the both pretreatment differently affected the protective effect of apigenin on hepatocytes. The former completely canceled the protective effect, whereas the latter did not. These findings further demonstrate that apigenin can exert a protective effect on D-GalN/LPS-induced hepatocellular injury via the increment of Nrf-2 nucleus translocation, which may increase the SOD and CAT levels and PPARγ protein expression and subsequently inhibit the inflammatory response.
Keywords: Apigenin; CAT; Hepatocytes; Nrf-2; PPARγ; SOD.