Abstract
The natural polyphenol compound resveratrol (RSV) is considered to have a broad spectrum of beneficial biological activities upon human health. However, the exact effect of RSV on steatosis (a phenotype of non-alcoholic fatty liver [NAFL]) or fibrosis and inflammation (major phenotypes of non-alcoholic steatohepatitis [NASH]) is not known. Our data showed that administration of RSV (2 or 20 mg/kg/day) did not suppress steatosis in a high-fat diet-induced model of NAFL in mice. In contrast, identical concentrations of RSV dramatically inhibited inflammation and fibrosis in a low-dose lipopolysaccharide-induced model of NASH. These data suggested that RSV administration-mediated improvement of inflammation and fibrosis was due to the inhibition of LPS reactivity controlled by CD14 expression in Kupffer cells. These findings suggest that RSV could be a candidate agent for the treatment of NASH.
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Cell Line
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Disease Models, Animal*
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Fibrosis / genetics
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Fibrosis / metabolism
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Fibrosis / prevention & control
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Fluorescent Antibody Technique
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Gene Expression / drug effects
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Humans
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Immunoblotting
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Inflammation / genetics
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Inflammation / metabolism
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Inflammation / prevention & control*
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Lipopolysaccharide Receptors / genetics
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Lipopolysaccharide Receptors / metabolism
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Lipopolysaccharides
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Male
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Mice, Inbred C57BL
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Non-alcoholic Fatty Liver Disease / chemically induced
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Non-alcoholic Fatty Liver Disease / genetics
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Non-alcoholic Fatty Liver Disease / prevention & control*
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Resveratrol
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Reverse Transcriptase Polymerase Chain Reaction
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STAT3 Transcription Factor / metabolism
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Signal Transduction / drug effects
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Stilbenes / pharmacology*
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Interleukin-6
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Lipopolysaccharide Receptors
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Lipopolysaccharides
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STAT3 Transcription Factor
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Stilbenes
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Tumor Necrosis Factor-alpha
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Resveratrol