期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 109, 期 -, 页码 1306-1312出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2018.10.196
关键词
trans-Chalcone; NASH; SREBPs; FAS; PPARs; Liver
资金
- Drug Applied Research Center of Tabriz University of Medical Sciences, Tabriz, Iran
Non-alcoholic steatohepatitis (NASH) is an inflammatory and progressive form of non-alcoholic fatty liver disease. However, there are no FDA-approved drugs for this condition. Lipids accumulated in NASH have a direct role in the progression of this disease. Therefore, this study for the first time explored the preventive effect of trans-chalcone on NASH through the modulation of sterol regulatory element binding protein (SREBP)-1c, SREBP-2, hepatic fatty acid synthesis (FAS) enzyme, proliferator-activated receptor (PPAR)-alpha, and PPAR-gamma 2 levels, which are involved in hepatic lipid metabolism. In this study, male rats were randomly divided into three groups (n = 7): Control, received 10% tween 80; NASH, received 10% tween 80 and 10 ml/kg high-fat emulsion (high-fat diet, HFD); and NASH + TC, received 20 mg/kg trans-chalcone and 10 ml/kg HFD. All treatments were performed by once-daily oral gavage for 6 weeks. Liver and blood samples were collected and serum levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol, as well as hepatic levels of SREBP-1c, SREBP-2, FAS, PPAR-alpha, and PPAR-gamma 2, were measured. Moreover, hematoxylin and eosin stained tissues were used for histological analysis. In this study, treatment of HFD-fed rats with trans-chalcone significantly reduced abnormalities in liver histology, serum levels of liver injury markers, liver index, and hepatic levels of SREBP-1c, SREBP-2, FAS, and PPAR-gamma 2. Furthermore, trans-chalcone significantly increased hepatic PPARa levels in these rats. Therefore, it seems that trans-chalcone protects the liver of HFD-fed rats against NASH development through reduction of SREBP-1c/ FAS-and PPAR-gamma 2-related lipogenesis, attenuation of SREBP-2-related cholesterol synthesis, and elevation of PPARa-related fatty acid oxidation.
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