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Preventive effect of trans-chalcone on non-alcoholic steatohepatitis: Improvement of hepatic lipid metabolism.
Biomed Pharmacother 2019; 109:1306-1312BP

Abstract

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)-α, and PPAR-γ2 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-α, and PPAR-γ2, 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-γ2. Furthermore, trans-chalcone significantly increased hepatic PPARα 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-γ2-related lipogenesis, attenuation of SREBP-2-related cholesterol synthesis, and elevation of PPARα-related fatty acid oxidation.

Authors+Show Affiliations

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: alipourmr@tbzmed.ac.ir.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30551380

Citation

Karimi-Sales, Elham, et al. "Preventive Effect of Trans-chalcone On Non-alcoholic Steatohepatitis: Improvement of Hepatic Lipid Metabolism." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 109, 2019, pp. 1306-1312.
Karimi-Sales E, Ebrahimi-Kalan A, Alipour MR. Preventive effect of trans-chalcone on non-alcoholic steatohepatitis: Improvement of hepatic lipid metabolism. Biomed Pharmacother. 2019;109:1306-1312.
Karimi-Sales, E., Ebrahimi-Kalan, A., & Alipour, M. R. (2019). Preventive effect of trans-chalcone on non-alcoholic steatohepatitis: Improvement of hepatic lipid metabolism. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 109, pp. 1306-1312. doi:10.1016/j.biopha.2018.10.196.
Karimi-Sales E, Ebrahimi-Kalan A, Alipour MR. Preventive Effect of Trans-chalcone On Non-alcoholic Steatohepatitis: Improvement of Hepatic Lipid Metabolism. Biomed Pharmacother. 2019;109:1306-1312. PubMed PMID: 30551380.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preventive effect of trans-chalcone on non-alcoholic steatohepatitis: Improvement of hepatic lipid metabolism. AU - Karimi-Sales,Elham, AU - Ebrahimi-Kalan,Abbas, AU - Alipour,Mohammad Reza, Y1 - 2018/11/09/ PY - 2018/08/14/received PY - 2018/10/25/revised PY - 2018/10/31/accepted PY - 2018/12/16/entrez PY - 2018/12/16/pubmed PY - 2019/3/29/medline KW - FAS, PPARs KW - Liver KW - NASH KW - SREBPs KW - trans-Chalcone SP - 1306 EP - 1312 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 109 N2 - 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)-α, and PPAR-γ2 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-α, and PPAR-γ2, 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-γ2. Furthermore, trans-chalcone significantly increased hepatic PPARα 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-γ2-related lipogenesis, attenuation of SREBP-2-related cholesterol synthesis, and elevation of PPARα-related fatty acid oxidation. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/30551380/Preventive_effect_of_trans_chalcone_on_non_alcoholic_steatohepatitis:_Improvement_of_hepatic_lipid_metabolism_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(18)35691-9 DB - PRIME DP - Unbound Medicine ER -