Xanthohumol, the major prenylated
chalcone found in hops, is known for its anti-inflammatory properties. We have recently shown that
xanthohumol inhibits hepatic
inflammation and
fibrosis in a murine model of
nonalcoholic steatohepatitis. The aim of this study was to investigate the effect of
xanthohumol in an acute model of liver injury.
Carbon tetrachloride (CCl(4)), an industrial
solvent, is a hepatotoxic agent and its administration is widely used as an animal model of toxin-induced liver injury.
Xanthohumol was applied orally at a dose of 1 mg/g
body weight 2 days prior as well as during and after exposure to CCl(4). 72 h after a single CCl(4) application histomorphology and serum levels of
transaminases revealed considerable hepatocellular
necrosis, which was accompanied by significantly enhanced hepatic expression of pro-inflammatory
cytokines. Furthermore, elevated hepatic alpha-smooth muscle actin expression indicated activation of hepatic stellate cells, and in accordance, we detected enhanced hepatic expression levels of TGF-β and
collagen type I reflecting a marked fibrogenic response to CCl(4) exposure. While the degree of hepatocellular damage in response to CCl(4) was similar in mice which received
xanthohumol and the control group, pro-inflammatory and profibrogenic hepatic gene expression were almost completely blunted in
xanthohumol fed mice. Furthermore,
xanthohumol fed mice revealed decreased hepatic NFκB activity. These results suggest that the protective effects of
xanthohumol in this toxic liver injury model involves direct mechanisms related to its ability to block both hepatic
inflammation and the activation of hepatic stellate cells, presumable at least in part via decreasing NFκB activity. Thus, this study further indicates the potential of
xanthohumol application to prevent or ameliorate the development and progression of
liver fibrosis in response to hepatic injury.