Objective: To investigate the protective effect and underlying mechanism of genistein from Hydrococyle sibthorpioides on lipopolysaccharide (LPS)/D-galactosamine (D-GalN) -induced acute hepatic injury in mice. Method: Male mice were randomly divided into normal group

model group

low-

middle-and high-doses of genistein-treated groups. The mice in the normal and model groups were given saline. The animals in the genistein-treated groups were administered intraperitoneally 0.5

1

2 mg · kg-1 genistein once daily for 3 days. At the end of treatment

except the mice in the normal group

all mice were intraperitoneally injected with 50 μg · kg-1 LPS plus 800 mg · kg-1 D-GalN. Blood samples were collected from mice eyes 1.5 h after LPS/D-GalN administration

then the mice were killed and liver samples were dissected out after 6 h. The activities of serum alanine aminotransferase(ALT)

aspartate aminotransferase(AST) and bilirubin

the contents of hepatic tumor necrosis factor-α(TNF-α)

nitric oxide(NO) and malandialdehyde(MDA)

as well as the expression of TNF-α

inducible nitric oxide synthase(iNOS)

nuclear factor(NF) -κB p65

Caspase-3 and B cell lymphoma/leukemia-2(Bcl-2) were detected. In addition

the damage of liver tissues was observed by light microscope. Result: Compared to the model control

treatment with genistein significantly decreased the AST and ALT activities

further increased the bilirubin level. Histologic examination showed that genistein markedly alleviated the mice livers tissue damage. Furthermore

genistein reduced the pro-inflammatory cytokines including TNF-α and NO/iNOS via inhibiting the NF-κB activity. In addition

genistein inhibited the expression of Caspase-3

enhanced levels of Bcl-2 and total bilirubin. Conclusion: Genistein could prevent LPS/D-GalN-induced acute liver damage in mice

and its underlying mechanisms were mainly due to its ability to block NF-κB signaling pathway for anti-inflammation response and attenuate hepatocellular apoptosis.