Resveratrol ameliorates fibrosis and inflammation in a mouse model of nonalcoholic steatohepatitis

• Published in: Scientific reports Vol. 6; no. 1; p. 22251
• Main Authors: Kessoku, Takaomi, Imajo, Kento, Honda, Yasushi, Kato, Takayuki, Ogawa, Yuji, Tomeno, Wataru, Kato, Shingo, Mawatari, Hironori, Fujita, Koji, Yoneda, Masato, Nagashima, Yoji, Saito, Satoru, Wada, Koichiro, Nakajima, Atsushi
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 25.02.2016
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; CD14 antigen; Cell Line; Disease Models, Animal; Fatty liver; Fibrosis; Fibrosis - genetics; Fibrosis - metabolism; Fibrosis - prevention & control; Fluorescent Antibody Technique; Gene Expression - drug effects; High fat diet; Humans; Immunoblotting; Inflammation; Inflammation - genetics; Inflammation - metabolism; Inflammation - prevention & control; Interleukin-6 - genetics; Interleukin-6 - metabolism; Kupffer cells; Lipopolysaccharide Receptors - genetics; Lipopolysaccharide Receptors - metabolism; Lipopolysaccharides; Male; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease - chemically induced; Non-alcoholic Fatty Liver Disease - genetics; Non-alcoholic Fatty Liver Disease - prevention & control; Resveratrol; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Signal Transduction - drug effects; STAT3 Transcription Factor - metabolism; Steatosis; Stilbenes - pharmacology; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep22251

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.