Z Gastroenterol 2012; 50 - P3_08
DOI: 10.1055/s-0031-1295849

Xanthohumol suppresses hepatic inflammatory response to warm ischemia-reperfusion injury

C Dorn 1, J Heilmann 2, C Hellerbrand 1
  • 1Department of Internal Medicine I, University Hospital Regensburg, Regensburg
  • 2Department of Pharmaceutical Biology, Institute of Pharmacy, Regensburg

Liver ischemia/reperfusion (I/R) leads to the formation of reactive oxygen species (ROS), which cause liver injury and initiate an inflammatory response, a critical problem after liver surgery and transplantation. Xanthohumol, the major prenylated chalcone found in hops, is known for its anti-inflammatory and ROS-scavenging properties.

The aim of this study was to investigate the effect of xanthohumol in a model of warm ischemia-reperfusion liver injury.

Methods and Results: Xanthohumol was applied to BALB/c mice orally at a dose of 1mg/g body weight for 5 days before warm ischemia/reperfusion (I/R) injury was induced by clamping the vascular blood supply to the median and left lateral liver lobes for 1h followed by a 6h period of reperfusion. Hepatic HMOX–1 mRNA expression, a sensitive indicator of oxidative injury, was highly increased and hepatic glutathione content was significantly decreased after I/R. Histomorphology and serum levels of transaminases revealed considerable hepatocellular necrosis, which was accompanied by significantly enhanced hepatic expression of pro-inflammatory cytokines and elevated NFkappaB activity. While GSH-depletion and induction of hepatic HMOX–1 expression after I/R was significantly blunted in xanthohumol-fed mice compared to control diet-fed mice, the degree of overall hepatocellular damage in response to I/R was similar in both groups. However, pro-inflammatory hepatic gene expression as well as induction of NFkappaB activity was almost completely blunted in xanthohumol fed mice.

Conclusions: Our data suggest that xanthohumol is able to counter hepatic oxidative stress in vivo, and more importantly, block the inflammatory response to I/R induced liver damage, presumable at least in part via decreasing NFkappaB activity. Thus, this study indicates the potential of xanthohumol application to prevent adverse inflammatory responses to I/R induced liver damage, e.g. after surgical liver resection or transplantation.