Xanthohumol improves glucose tolerance and inhibits hepatic steatosis, inflammation and fibrogenesis in a murine model of non-alcoholic steatohepatitis

Xanthohumol, the principal prenylated flavonoid of the female inflorescences of the hop plant, has been most extensively studied as cancer chemopreventive agent. In addition, anti-inflammatory properties have been demonstrated in various organs including the liver. Nonalcoholic fatty liver disease (NAFLD) is considered as hepatic manifestation of the metabolic syndrome, and in a subset of cases hepatic steatosis progresses to steatohepatitis (NASH), which may further advance with significant fibrosis.

The aim of this study was to investigate the effect of xanthohumol in a dietary murine model of obesity, hyperglycemia and non-alcoholic steatohepatitis.

Methods and Results: Feeding a high fat diet (HFD) to male 129S1/SvImJ mice for 24 weeks induced significant body weight gain, an impaired glucose tolerance and elevated fasting blood glucose levels. Supplementation of the HFD with 0.5%(w/w) xanthohumol didn’t affect food consumption but almost completely blunted the body weight gain and the increase of blood glucose levels, and markedly improved glucose tolerance. Furthermore, the HFD induced increase of hepatic triglyceride and serum transaminases levels were significantly lower in mice, which received xanthohumol in addition to the HFD. Moreover, the elevated hepatic expression of pro-inflammatory (TNF, MCP–1) and pro-fibrogenic (TGF-beta, TIMP–1) genes in response to HFD-feeding was significantly blunted by xanthohumol.

Conclusions: Xanthohumol prevented nutritionally induced obesity and diabetes as well hepatic steatosis, inflammation and fibrogenesis in mice. Previous studies have shown the safety of even long term application of hop extracts in man, and thus, our data indicate the potential of xanthohumol as a functional nutrient to fight the development of the metabolic syndrome and fatty liver diseases.