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Int J Clin Exp Pathol 2012;5(1):29-36

Original Article
Protective effect of xanthohumol on toxin-induced liver inflammation and fibrosis

Christoph Dorn, Jörg Heilmann, Claus Hellerbrand

Department of Internal Medicine I, University Hospital Regensburg, Germany; Institute of Pharmacy, University of Regensburg, Germany

Received November 1, 2011; accepted December 6, 2011; Epub January 1, 2012; published January 15, 2012

Abstract: 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 non-alcoholic steatohepatitis. The aim of this study was to
investigate the effect of xanthohumol in an acute model of liver injury. Carbon tetrachloride (CCl4), 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 CCl4. 72 h after a single CCl4 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- and collagen type I reflecting a marked fibrogenic response to CCl4
exposure. While the degree of hepatocellular damage in response to CCl4 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 NFB 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 NFB 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. (IJCEP1111001).

Keywords: Xanthohumol, carbon tetrachloride, fibrosis, inflammation, acute liver injury

Address all correspondence to:
Claus Hellerbrand, M.D.
Department of Internal Medicine I
University of Regensburg
D-93053 Regensburg
Tel: +49-941-944-7155
Fax.:    +49-941-944-7154
E-mail: claus.hellerbrand@klinik.uni-regensburg.de