Xanthohumol, a chalcon derived from hops, inhibits hepatic inflammation and fibrosis

Xanthohumol (XN) is a major prenylated chalcone found in hops, which is used to add bitterness and flavor to beer. In this study, we first investigated the effects of XN on hepatocytes and hepatic stellate cells (HSC), the central mediators of liver fibrogenesis. XN inhibited the activation of primary human HSC and induced apoptosis in activated HSC in vitro in a dose dependent manner (0-20 mu M). In contrast, XN doses as high as 50 mM did not impair viability of primary human hepatocytes. However, in both cell types XN inhibited activation of the transcription factor NF kappa B and expression of NF kappa B dependent proinflammatory genes. In vivo, feeding of XN reduced hepatic inflammation and expression of profibrogenic genes in a murine model of non-alcoholic steatohepatitis. These data indicate that XN has the potential as functional nutrient for the prevention or treatment of nonalcoholic steatohepatitis or other chronic liver disease.