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...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-11-01
|
Series: | Nutrients |
Subjects: | |
Online Access: | https://www.mdpi.com/2072-6643/13/11/4155 |
_version_ | 1797508926389878784 |
---|---|
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 |
collection | DOAJ |
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. |
first_indexed | 2024-03-10T05:10:46Z |
format | Article |
id | doaj.art-48026bd2102d4f2093d9b906f422e390 |
institution | Directory Open Access Journal |
issn | 2072-6643 |
language | English |
last_indexed | 2024-03-10T05:10:46Z |
publishDate | 2021-11-01 |
publisher | MDPI AG |
record_format | Article |
series | Nutrients |
spelling | doaj.art-48026bd2102d4f2093d9b906f422e3902023-11-23T00:51:30ZengMDPI AGNutrients2072-66432021-11-011311415510.3390/nu13114155Chlorogenic Acid Protects against Advanced Alcoholic Steatohepatitis in Rats via Modulation of Redox Homeostasis, Inflammation, and LipogenesisVyacheslav Buko0Ilya Zavodnik1Grażyna Budryn2Małgorzata Zakłos-Szyda3Elena Belonovskaya4Siarhei Kirko5Dorota Żyżelewicz6Agnieszka Zakrzeska7Aliaksei Bakunovich8Viktor Rusin9Valentina Moroz10Division of Biochemical Pharmacology, Institute of Biochemistry of Biologically Active Compounds, National Academy of Sciences, BLK, 50, 230030 Grodno, BelarusDepartment of Biochemistry, Yanka Kupala State University of Grodno, Ozheshko 22, 230023 Grodno, BelarusInstitute of Food Technology and Analysis, Lodz University of Technology, Stefanowskiego 2/22, 90-537 Lodz, PolandInstitute of Molecular and Industrial Biotechnology, Lodz University of Technology, Stefanowskiego 2/22, 90-537 Lodz, PolandDivision of Biochemical Pharmacology, Institute of Biochemistry of Biologically Active Compounds, National Academy of Sciences, BLK, 50, 230030 Grodno, BelarusDivision of Biochemical Pharmacology, Institute of Biochemistry of Biologically Active Compounds, National Academy of Sciences, BLK, 50, 230030 Grodno, BelarusInstitute of Food Technology and Analysis, Lodz University of Technology, Stefanowskiego 2/22, 90-537 Lodz, PolandDepartment of Biotechnology, University of Medical Sciences, Krakowska 9, 15-875 Bialystok, PolandDivision of Biochemical Pharmacology, Institute of Biochemistry of Biologically Active Compounds, National Academy of Sciences, BLK, 50, 230030 Grodno, BelarusThe 2nd Department of Surgical Diseases, Grodno State Medical University, Gorkogo 80, 230009 Grodno, BelarusDivision of Biochemical Pharmacology, Institute of Biochemistry of Biologically Active Compounds, National Academy of Sciences, BLK, 50, 230030 Grodno, BelarusThe 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.https://www.mdpi.com/2072-6643/13/11/4155in vivo studyalcoholic steatohepatitisoxidative stressinflammatory responsechlorogenic acid |
spellingShingle | 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 Nutrients in vivo study alcoholic steatohepatitis oxidative stress inflammatory response chlorogenic acid |
title | 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_short | 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 |
topic | in vivo study alcoholic steatohepatitis oxidative stress inflammatory response chlorogenic acid |
url | https://www.mdpi.com/2072-6643/13/11/4155 |
work_keys_str_mv | AT vyacheslavbuko chlorogenicacidprotectsagainstadvancedalcoholicsteatohepatitisinratsviamodulationofredoxhomeostasisinflammationandlipogenesis AT ilyazavodnik chlorogenicacidprotectsagainstadvancedalcoholicsteatohepatitisinratsviamodulationofredoxhomeostasisinflammationandlipogenesis AT grazynabudryn chlorogenicacidprotectsagainstadvancedalcoholicsteatohepatitisinratsviamodulationofredoxhomeostasisinflammationandlipogenesis AT małgorzatazakłosszyda chlorogenicacidprotectsagainstadvancedalcoholicsteatohepatitisinratsviamodulationofredoxhomeostasisinflammationandlipogenesis AT elenabelonovskaya chlorogenicacidprotectsagainstadvancedalcoholicsteatohepatitisinratsviamodulationofredoxhomeostasisinflammationandlipogenesis AT siarheikirko chlorogenicacidprotectsagainstadvancedalcoholicsteatohepatitisinratsviamodulationofredoxhomeostasisinflammationandlipogenesis AT dorotazyzelewicz chlorogenicacidprotectsagainstadvancedalcoholicsteatohepatitisinratsviamodulationofredoxhomeostasisinflammationandlipogenesis AT agnieszkazakrzeska chlorogenicacidprotectsagainstadvancedalcoholicsteatohepatitisinratsviamodulationofredoxhomeostasisinflammationandlipogenesis AT aliakseibakunovich chlorogenicacidprotectsagainstadvancedalcoholicsteatohepatitisinratsviamodulationofredoxhomeostasisinflammationandlipogenesis AT viktorrusin chlorogenicacidprotectsagainstadvancedalcoholicsteatohepatitisinratsviamodulationofredoxhomeostasisinflammationandlipogenesis AT valentinamoroz chlorogenicacidprotectsagainstadvancedalcoholicsteatohepatitisinratsviamodulationofredoxhomeostasisinflammationandlipogenesis |