Xanthohumol inhibits the development of non-alcoholic steatohepatitis by systemic as well as direct effects on hepatocellular lipid uptake

There is growing interest in phenolic compounds and their presumed role in the prevention of various degenerative diseases. 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 in vitro and in vivo models of hepatic steatosis induced inflammation.

Methods and Results: Incubation of primary human hepatocytes with BSA-complexed oleate lead to free fatty acid (FFA) and triglyceride accumulation, ROS-formation and proinflammatory gene expression in primary human hepatocytes (PHH), and these effects were inhibited by preincubation with Xanthohumol in a dose dependent manner. Feeding a high fat diet (HFD) to 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 almost completely blunted these metabolic alterations. 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 NAFLD.