Cinnamon extract protects against acute alcohol-induced liver steatosis in mice.
Acute and chronic consumption of alcohol can cause increased intestinal permeability and bacterial overgrowth, thereby increasing portal endotoxin levels. This barrier impairment subsequently leads to an activation of hepatic Kupffer cells and increased release of reactive oxygen species as well as of tumor necrosis factor-alpha (TNFalpha). Recent studies have suggested that cinnamon extract may have antiinflammatory effects. In the present study, the protective effects of an alcoholic extract of cinnamon bark was assessed in a mouse model of acute alcohol-induced steatosis and in RAW 264.7 macrophages, used here as a model of Kupffer cells. Acute alcohol ingestion caused a >20-fold increase in hepatic lipid accumulation. Pretreatment with cinnamon extract significantly reduced the hepatic lipid accumulation. This protective effect of cinnamon extract was associated with an inhibition of the induction of the myeloid differentiation primary response gene (MyD) 88, inducible nitric oxide (NO) synthase (iNOS), and plasminogen activator inhibitor 1 mRNA expression found in livers of alcohol-treated animals. In vitro prechallenge with cinnamon extract suppressed lipopolysaccharide (LPS)-induced MyD88, iNOS, and TNFalpha expression as well as NO formation almost completely. Furthermore, LPS treatment of RAW 264.7 macrophages further resulted in degradation of inhibitor kappaB; this effect was almost completely blocked by cinnamon extract. Taken together, our data show that an alcohol extract of cinnamon bark may protect the liver from acute alcohol-induced steatosis through mechanisms involving the inhibition of MyD88 expression.
Kanuri
Giridhar
G
Department of Nutritional Medicine, University of Hohenheim, D-70599 Stuttgart, Germany.
Weber
Synia
S
Volynets
Valentina
V
Spruss
Astrid
A
Bischoff
Stephan C
SC
Bergheim
Ina
I
D000818:Animals; D002460:Cell Line; D002935:Cinnamomum zeylanicum / Q000737:chemistry*; D000431:Ethanol / Q000633:toxicity*; D005234:Fatty Liver / Q000139:chemically induced* / Q000517:prevention & control*; D005786:Gene Expression Regulation / Q000187:drug effects; D008264:Macrophages; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D058258:Serpin E2; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D010936:Plant Extracts; D012333:RNA, Messenger; D058258:Serpin E2; C511869:Serpine2 protein, mouse; D015843:Serpins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000431:Ethanol; D052247:Nitric Oxide Synthase Type II