Xanthohumol, a chalcon derived from hops, inhibits hepatic inflammation and fibrosis.
Xanthohumol (XN) is a major prenylated chalcone found in hops, which is used to add bitterness and flavor to beer. In this study, we first investigated the effects of XN on hepatocytes and hepatic stellate cells (HSC), the central mediators of liver fibrogenesis. XN inhibited the activation of primary human HSC and induced apoptosis in activated HSC in vitro in a dose dependent manner (0-20 microM). In contrast, XN doses as high as 50 microM did not impair viability of primary human hepatocytes. However, in both cell types XN inhibited activation of the transcription factor NFkappaB and expression of NFkappaB dependent proinflammatory genes. In vivo, feeding of XN reduced hepatic inflammation and expression of profibrogenic genes in a murine model of non-alcoholic steatohepatitis. These data indicate that XN has the potential as functional nutrient for the prevention or treatment of non-alcoholic steatohepatitis or other chronic liver disease.
Dorn
Christoph
C
Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.
Kraus
Birgit
B
Motyl
Magdalena
M
Weiss
Thomas S
TS
Gehrig
Manfred
M
Schölmerich
Jürgen
J
Heilmann
Jörg
J
Hellerbrand
Claus
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005234:Fatty Liver / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D035264:Flowers / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D027582:Humulus / Q000737:chemistry*; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D009994:Osmolar Concentration; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011427:Propiophenones / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D005419:Flavonoids; D016328:NF-kappa B; D010936:Plant Extracts; D011427:Propiophenones; D012333:RNA, Messenger; C104536:xanthohumol