C57BL/6 마우스에서 고지방 식이와 CCl4로 유발한 간섬유증에 미치는 커큐민의 보호효과
Protective Effects of Curcumin on CCl4-Induced Hepatic Fibrosis with High Fat Diet in C57BL/6 Mice
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Curcumin, a major polyphenolic compound of turmeric, is well known to prevent non-alcoholic steatohepatitis (NASH) related to obesity. The aim of the study was to investigate the effect of curcumin on hepatic fibrosis induced by carbon tetrachloride (CCl4) in obese mice. CCl4 was administrated in mice fed a normal diet (ND) or a high fat diet (HFD) for 7 weeks together with or without curcumin. It was conducted to examine for metabolic profiles, adipocyte size, and liver fibrosis by serum biochemistry, histology and immunohistochemistry. Also, Apoptosis of hepatic cells was determined by the TUNEL method. Treatment with curcumin significantly lowered the body weight, fasting glucose, serum AST and ALT, and decreased the adipocyte size, the number of macrophage and mast cells in adipose tissue, and collagen deposition in liver tissue in the HFD+CCl4 group compared with the findings of the HFD+CCl4 group. In contrast, treatment with curcumin on the ND+CCl4 group did not show a significant difference except the body weight and mast cell number when compared with the ND+CCl4 group. Furthermore, curcumin significantly reduced the number of parenchymal apoptotic cells, whereas it increased the number of non-pa-renchymal apoptotic cells, especially resembling an activated hepatic stellate cell in the liver. Taken together, this data suggests that curcumin might be an effective antifibrotic drug for the prevention of liver disease progression in obese mice. Thus, the development of curcumin as a therapy for obesity and liver fibrosis is supported.
Abstract
Curcumin, a major polyphenolic compound of turmeric, is well known to prevent non-alcoholic steatohepatitis (NASH) related to obesity. The aim of the study was to investigate the effect of curcumin on hepatic fibrosis induced by carbon tetrachloride (CCl4) in obese mice. CCl4 was administrated in mice fed a normal diet (ND) or a high fat diet (HFD) for 7 weeks together with or without curcumin. It was conducted to examine for metabolic profiles, adipocyte size, and liver fibrosis by serum biochemistry, histology and immunohistochemistry. Also, Apoptosis of hepatic cells was determined by the TUNEL method. Treatment with curcumin significantly lowered the body weight, fasting glucose, serum AST and ALT, and decreased the adipocyte size, the number of macrophage and mast cells in adipose tissue, and collagen deposition in liver tissue in the HFD+CCl4 group compared with the findings of the HFD+CCl4 group. In contrast, treatment with curcumin on the ND+CCl4 group did not show a significant difference except the body weight and mast cell number when compared with the ND+CCl4 group. Furthermore, curcumin significantly reduced the number of parenchymal apoptotic cells, whereas it increased the number of non-pa-renchymal apoptotic cells, especially resembling an activated hepatic stellate cell in the liver. Taken together, this data suggests that curcumin might be an effective antifibrotic drug for the prevention of liver disease progression in obese mice. Thus, the development of curcumin as a therapy for obesity and liver fibrosis is supported.
참고문헌 (25)
- Aggarwal BB, "Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases", Int J Biochem Cell Biol, 41, pp.40~59 (2009)
- Aggarwal BB, "Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets", Trends Pharmacol Sci, 30, pp.85~94 (2009)
- Altintas MM, "Mast cells, macrophages, and crown-like structures distinguish subcutaneous from visceral fat in mice", J Lipid Res, 52, pp.480~488 (2011)
- Bruck R, "Prevention of liver cirrhosis in rats by curcumin", Liver Int, 27, pp.373~383 (2007)
- Charlton M, "Fast food diet mouse: novel small animal model of NASH with ballooning, progressive fibrosis, and high physiological fidelity to the human condition", Am J Physiol Gastrointest Liver Physiol, 301, pp.825~834 (2011)
- Chheda TK, "Fast food diet with CCl4 micro-dose induced hepatic fibrosis -a novel animal model", BMC Gastroenterol, 14, pp.89~97 (2014)
- Farrell GC, "Nonalcoholic fatty liver disease: from steatosis to cirrhosis", Hepatology, 43, pp.99~112 (2006)
- Fu Y, "Curcumin protects the rat liver from CCl4-caused injury and fibrogenesis by attenuating oxidative stress and suppressing inflammation", Mol Pharmacol, 73, pp.399~409 (2008)
- Hernandez-Gea V, "Pathogenesis of liver fibrosis", Annu Rev Pathol, 6, pp.425~456 (2011)
- Ito M, "Longitudinal analysis of murine steatohepatitis model induced by chronic exposure to high-fat diet", Hepatol Res, 37, pp.50~57 (2007)
- Kang HC, "Curcumin inhibits collagen synthesis and hepatic stellate cell activation in-vivo and in-vitro", J Pharm Pharmacol, 54, pp.119~126 (2002)
- Kamalakkannan N, "Comparative effects of curcumin and an analogue of curcumin in carbon tetrachloride-induced hepatotoxicity in rats", Basic Clin Pharmacol Toxicol, 97, pp.15~21 (2005)
- 임용, "세포독성을 일으키는 Bleomycin과 Cyclophosphamide에 녹차 카테킨이 미치는 보호적인 효과", 대한임상검사과학회지, 46(2), pp.75~78 (2014), 대한임상검사과학회[DOI]
- Lubbad A, "Curcumin attenuates inflammation through inhibition of TLR-4 receptor in experimental colitis", Mol Cell Biochem, 322, pp.127~135 (2009)
- Nakamura A, "Lessons from mouse models of high-fat diet-induced NAFLD", Int J Mol Sci, 14, pp.21240~21257 (2013)
- Park EJ, "Protective effect of curcumin in rat liver injury induced by carbon tetrachloride", J Pharm Pharmacol, 52, pp.437~440 (2000)
- Priya S, "Cell survival, activation and apoptosis of hepatic stellate cells: modulation by extracellular matrix proteins", Hepatol Res, 38, pp.1221~1232 (2008)
- Shoelson SE, "Inflammation and insulin resistance", J Clin Invest, 116, pp.1793~1801 (2006)
- Shao W, "Curcumin prevents high fat diet induced insulin resistance and obesity via attenuating lipogenesis in liver and inflammatory pathway in adipocytes", PLoS One, 7(1), pp.e28784~ (2012)
- Sharma RA, "Effects of dietary curcumin on glutathione S-transferase and malondialdehyde-DNA adducts in rat liver and colon mucosa: relationship with drug levels", Clin Cancer Res, 7, pp.1452~1458 (2001)
- 심문정, "대사증후군 구성요소와 우울증, 스트레스 사이의 관계", 대한임상검사과학회지, 46(2), pp.67~74 (2014), 대한임상검사과학회[DOI]
- Wang Y, "Dietary supplementation of blueberry juice enhances hepatic expression of metallothionein and attenuates liver fibrosis in rats", PLoS One, 8(3), pp.e58659~ (2013)
- Weber LW, "Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model", Crit Rev Toxicol, 33, pp.105~136 (2003)
- Weisberg SP, "Dietary curcumin significantly improves obesity-associated inflammation and diabetes in mouse models of diabesity", Endocrinology, 149, pp.3549~3558 (2008)
- Yamauchi T, "The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity", Nat Med, 7, pp.941~946 (2001)