Chlorogenic Acid Protects against Advanced Alcoholic Steatohepatitis in Rats via Modulation of Redox Homeostasis, Inflammation, and Lipogenesis

The aim of this study was to evaluate the therapeutic effects of chlorogenic acid (CGA) in rats with advanced alcoholic steatohepatitis. The rats were fed on a high-fat diet and gavaged with ethanol (4 g/kg) for 8 weeks. The livers of ethanol-treated rats showed steatosis; necrosis and mononuclear i...

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Autores principales:	Vyacheslav Buko, Ilya Zavodnik, Grażyna Budryn, Małgorzata Zakłos-Szyda, Elena Belonovskaya, Siarhei Kirko, Dorota Żyżelewicz, Agnieszka Zakrzeska, Aliaksei Bakunovich, Viktor Rusin, Valentina Moroz
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	in vivo study alcoholic steatohepatitis oxidative stress inflammatory response chlorogenic acid Nutrition. Foods and food supply TX341-641
Acceso en línea:	https://doaj.org/article/48026bd2102d4f2093d9b906f422e390
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spelling	oai:doaj.org-article:48026bd2102d4f2093d9b906f422e3902021-11-25T18:37:11ZChlorogenic Acid Protects against Advanced Alcoholic Steatohepatitis in Rats via Modulation of Redox Homeostasis, Inflammation, and Lipogenesis10.3390/nu131141552072-6643https://doaj.org/article/48026bd2102d4f2093d9b906f422e3902021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6643/13/11/4155https://doaj.org/toc/2072-6643The aim of this study was to evaluate the therapeutic effects of chlorogenic acid (CGA) in rats with advanced alcoholic steatohepatitis. The rats were fed on a high-fat diet and gavaged with ethanol (4 g/kg) for 8 weeks. The livers of ethanol-treated rats showed steatosis; necrosis and mononuclear infiltration; and significant upregulation of the mRNA expression of the prooxidant (Cyp2e1, iNos), lipogenic (Srebp1, Acc), proinflammatory (Tlr4, Nf-κb, TnfA, Il-1B, and Il-6), and profibrogenic (TgfB, Col1, VegfA) genes. Simultaneously, a downregulation of level of <i>Sod</i> and <i>Nrf2</i> was observed, which was accompanied by increased serum transaminase, TnfA, and serum and liver triglycerides levels. CGA administration (40 and 80 mg/kg, 8 weeks) to ethanol-fed group reduced the liver expression levels of <i>Cyp2e1</i> and <i>iNos</i>, whereas it markedly enhanced the expression of <i>Sod</i>, <i>Nrf2</i>, and <i>Ho-1</i>. CGA at both doses downregulated the expressions of lipogenic, proinflammatory, and profibrogenic genes, while the expression of <i>Tlr4</i> was lowered only after the higher dose of CGA. The higher dose of CGA efficiently prevented the progression of alcohol-induced steatosis and reduced inflammation through regulation of the expression of genes encoding the proteins involved in the Tlr4/Nf-κB signaling pathway and fibrosis. The study revealed hepatoprotective and anti-inflammatory effects of CGA through the regulation of expression of genes encoding Cyp2e1/Nrf2 involved in oxidative stress modulation. These results demonstrate CGA as a therapeutic candidate for the prevention and treatment of alcoholic steatohepatitis.Vyacheslav BukoIlya ZavodnikGrażyna BudrynMałgorzata Zakłos-SzydaElena BelonovskayaSiarhei KirkoDorota ŻyżelewiczAgnieszka ZakrzeskaAliaksei BakunovichViktor RusinValentina MorozMDPI AGarticlein vivo studyalcoholic steatohepatitisoxidative stressinflammatory responsechlorogenic acidNutrition. Foods and food supplyTX341-641ENNutrients, Vol 13, Iss 4155, p 4155 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	in vivo study alcoholic steatohepatitis oxidative stress inflammatory response chlorogenic acid Nutrition. Foods and food supply TX341-641
spellingShingle	in vivo study alcoholic steatohepatitis oxidative stress inflammatory response chlorogenic acid Nutrition. Foods and food supply TX341-641 Vyacheslav Buko Ilya Zavodnik Grażyna Budryn Małgorzata Zakłos-Szyda Elena Belonovskaya Siarhei Kirko Dorota Żyżelewicz Agnieszka Zakrzeska Aliaksei Bakunovich Viktor Rusin Valentina Moroz Chlorogenic Acid Protects against Advanced Alcoholic Steatohepatitis in Rats via Modulation of Redox Homeostasis, Inflammation, and Lipogenesis
description	The aim of this study was to evaluate the therapeutic effects of chlorogenic acid (CGA) in rats with advanced alcoholic steatohepatitis. The rats were fed on a high-fat diet and gavaged with ethanol (4 g/kg) for 8 weeks. The livers of ethanol-treated rats showed steatosis; necrosis and mononuclear infiltration; and significant upregulation of the mRNA expression of the prooxidant (Cyp2e1, iNos), lipogenic (Srebp1, Acc), proinflammatory (Tlr4, Nf-κb, TnfA, Il-1B, and Il-6), and profibrogenic (TgfB, Col1, VegfA) genes. Simultaneously, a downregulation of level of <i>Sod</i> and <i>Nrf2</i> was observed, which was accompanied by increased serum transaminase, TnfA, and serum and liver triglycerides levels. CGA administration (40 and 80 mg/kg, 8 weeks) to ethanol-fed group reduced the liver expression levels of <i>Cyp2e1</i> and <i>iNos</i>, whereas it markedly enhanced the expression of <i>Sod</i>, <i>Nrf2</i>, and <i>Ho-1</i>. CGA at both doses downregulated the expressions of lipogenic, proinflammatory, and profibrogenic genes, while the expression of <i>Tlr4</i> was lowered only after the higher dose of CGA. The higher dose of CGA efficiently prevented the progression of alcohol-induced steatosis and reduced inflammation through regulation of the expression of genes encoding the proteins involved in the Tlr4/Nf-κB signaling pathway and fibrosis. The study revealed hepatoprotective and anti-inflammatory effects of CGA through the regulation of expression of genes encoding Cyp2e1/Nrf2 involved in oxidative stress modulation. These results demonstrate CGA as a therapeutic candidate for the prevention and treatment of alcoholic steatohepatitis.
format	article
author	Vyacheslav Buko Ilya Zavodnik Grażyna Budryn Małgorzata Zakłos-Szyda Elena Belonovskaya Siarhei Kirko Dorota Żyżelewicz Agnieszka Zakrzeska Aliaksei Bakunovich Viktor Rusin Valentina Moroz
author_facet	Vyacheslav Buko Ilya Zavodnik Grażyna Budryn Małgorzata Zakłos-Szyda Elena Belonovskaya Siarhei Kirko Dorota Żyżelewicz Agnieszka Zakrzeska Aliaksei Bakunovich Viktor Rusin Valentina Moroz
author_sort	Vyacheslav Buko
title	Chlorogenic Acid Protects against Advanced Alcoholic Steatohepatitis in Rats via Modulation of Redox Homeostasis, Inflammation, and Lipogenesis
title_short	Chlorogenic Acid Protects against Advanced Alcoholic Steatohepatitis in Rats via Modulation of Redox Homeostasis, Inflammation, and Lipogenesis
title_full	Chlorogenic Acid Protects against Advanced Alcoholic Steatohepatitis in Rats via Modulation of Redox Homeostasis, Inflammation, and Lipogenesis
title_fullStr	Chlorogenic Acid Protects against Advanced Alcoholic Steatohepatitis in Rats via Modulation of Redox Homeostasis, Inflammation, and Lipogenesis
title_full_unstemmed	Chlorogenic Acid Protects against Advanced Alcoholic Steatohepatitis in Rats via Modulation of Redox Homeostasis, Inflammation, and Lipogenesis
title_sort	chlorogenic acid protects against advanced alcoholic steatohepatitis in rats via modulation of redox homeostasis, inflammation, and lipogenesis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/48026bd2102d4f2093d9b906f422e390
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Chlorogenic Acid Protects against Advanced Alcoholic Steatohepatitis in Rats via Modulation of Redox Homeostasis, Inflammation, and Lipogenesis

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