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• W130442010 abstract "Xanthohumol is the major prenylated chalcone found in hops, and it has been shown to exhibit various biological effects. However, xanthohumol effects on liver cells or in liver diseases, respectively, are widely unknown.In the present work, first the effects of xanthohumol on hepatic stellate cells (HSC), the central mediators of liver fibrogenesis, were analyzed. Xanthohumol inhibited the activation of primary human HSC and induces apoptosis in activated HSC in vitro in a dose dependent manner (0-20 µM). In contrast, xanthohumol doses as high as 100 µM did not impair viability of primary human hepatocytes (PHH). However, in both cell types xanthohumol inhibited NF-kappaB activation and expression of NF-kappaB dependent proinflammatory chemokines. In vivo, feeding of xanthohumol reduced levels of serum transaminases and hepatic expression of proinflammatory genes in a murine model of non-alcoholic steatohepatitis (NASH). Moreover, xanthohumol treatment significantly inhibited hepatic expression of profibrogenic genes and activation of HSC in vivo. Next, xanthohumol effects on hepatocellular carcinoma (HCC) cells were investigated. Xanthohumol concentration of 25 µM induced apoptosis in two HCC cell lines (HepG2 and Huh7). Furthermore, xanthohumol repressed proliferation and migration, as well as TNF induced activation of the transcription factor NF-kappaB and interleukin-8 expression in both cell lines at even lower concentrations. Finally, to evaluate the safety profile of xanthohumol female BALB/c mice were fed with a xanthohumol enriched diet for three weeks, achieving a daily dose of approximately 1000 mg xanthohumol /kg body weight per day. Macroscopical and histopathological examination of liver, kidney, colon, lung, heart, spleen and thymus revealed no signs of xanthohumol-toxicity, and biochemical serum analysis confirmed normal organ function. Further, serum glucose levels and hepatic glycogen content as well as hepatic CYP2E1 mRNA expression levels were unaffected by xanthohumol treatment. In addition, also mRNA expression of several genes indicative of early hepatic inflammation and fibrosis, a hallmark of chronic liver injury, did not differ between xanthohumol treated and control mice. In conclusion, xanthohumol has the potential to ameliorate NASH induced liver injury as well as different pro-tumorigenic mechanisms known to promote HCC progression. Together with the good safety profile these data suggest the potential use of xanthohumol as a functional nutrient or therapeutic agent to prevent or treat chronic liver diseases like NASH or HCC." @default.
• W130442010 created "2016-06-24" @default.
• W130442010 creator A5031210648 @default.
• W130442010 date "2009-11-09" @default.
• W130442010 modified "2023-09-23" @default.
• W130442010 title "ANALYSIS OF THE EFFECTS OF XANTHOHUMOL ON HEPATIC HOMEOSTASIS, INFLAMMATION, FIBROSIS AND CANCEROGENESIS" @default.
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