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Hepatoprotective activity of chrysin is mediated through TNF-α in chemically-induced acute liver damage: An in vivo study and molecular modeling
Chrysin (5,7-dihydroxyflavone) is a naturally occurring flavonoid present at high levels in honey, propolis and numerous plant extracts. Chrysin is known to have hepatoprotective activity, however, the mechanisms by which it exerts this effect remain unclear. In the present study, the effects of chr...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443293/ https://www.ncbi.nlm.nih.gov/pubmed/28565752 http://dx.doi.org/10.3892/etm.2017.4181 |
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author | Hermenean, Anca Mariasiu, Teodora Navarro-González, Inmaculada Vegara-Meseguer, Josefina Miuțescu, Eftimie Chakraborty, Sandipan Pérez-Sánchez, Horacio |
author_facet | Hermenean, Anca Mariasiu, Teodora Navarro-González, Inmaculada Vegara-Meseguer, Josefina Miuțescu, Eftimie Chakraborty, Sandipan Pérez-Sánchez, Horacio |
author_sort | Hermenean, Anca |
collection | PubMed |
description | Chrysin (5,7-dihydroxyflavone) is a naturally occurring flavonoid present at high levels in honey, propolis and numerous plant extracts. Chrysin is known to have hepatoprotective activity, however, the mechanisms by which it exerts this effect remain unclear. In the present study, the effects of chrysin in carbon tetrachloride (CCl(4))-induced acute liver damage were investigated and the results used to infer a possible mechanism behind chrysin's hepatoprotective activity. Prior to an intraperitoneal injection of CCl4 (1 ml/kg) to induce acute liver damage, chrysin (50 mg/kg) was administered orally to mice for 7 days. The positive control group was given 50 mg/kg standardized silymarin, a well-studied hepatoprotective flavonoid. Twenty-four h following CCl4 administration, an increase in the activity levels of serum aspartate-amino-transferase and alanine-amino-transferase was found. This was accompanied by extended centrilobular necrosis, steatosis and an altered hepatocyte ultrastructure. In addition, CCl4-induced acute hepatotoxicity was associated with an increase in hepatic tumor necrosis factor-α (TNF-α) and α-smooth muscle actin (α-SMA) protein expression, which was significantly decreased in the livers of mice pre-treated with chrysin (P<0.001), similar to the results of the silymarin pre-treated group (P<0.001). Treatment with chrysin prior to CCl4 exposure significantly reduced the activity of enzymes used as biochemical markers of poor liver function compared with the group which did not receive pre-treatment (P<0.001). In addition, the results of histopathological and electron microscopy liver examination showed chrysin pre-treatment reduced the effects of CCl4 treatment. Molecular modeling results demonstrated that the hepatoprotective activity of chrysin is mediated through TNF-α, as it reduces soluble TNF-α generation via blocking TNF-α-converting enzyme activity. In conclusion, the results of the present study suggest that inflammatory pathways are activated in CCl4-induced acute liver damage, which are ameliorated by chrysin pre-treatment. This indicates that chrysin is a potent hepatoprotective agent, similarly to silymarin at the same dose, which has the potential to be a viable alternative to conventional hepatoprotective treatments. |
format | Online Article Text |
id | pubmed-5443293 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-54432932017-05-30 Hepatoprotective activity of chrysin is mediated through TNF-α in chemically-induced acute liver damage: An in vivo study and molecular modeling Hermenean, Anca Mariasiu, Teodora Navarro-González, Inmaculada Vegara-Meseguer, Josefina Miuțescu, Eftimie Chakraborty, Sandipan Pérez-Sánchez, Horacio Exp Ther Med Articles Chrysin (5,7-dihydroxyflavone) is a naturally occurring flavonoid present at high levels in honey, propolis and numerous plant extracts. Chrysin is known to have hepatoprotective activity, however, the mechanisms by which it exerts this effect remain unclear. In the present study, the effects of chrysin in carbon tetrachloride (CCl(4))-induced acute liver damage were investigated and the results used to infer a possible mechanism behind chrysin's hepatoprotective activity. Prior to an intraperitoneal injection of CCl4 (1 ml/kg) to induce acute liver damage, chrysin (50 mg/kg) was administered orally to mice for 7 days. The positive control group was given 50 mg/kg standardized silymarin, a well-studied hepatoprotective flavonoid. Twenty-four h following CCl4 administration, an increase in the activity levels of serum aspartate-amino-transferase and alanine-amino-transferase was found. This was accompanied by extended centrilobular necrosis, steatosis and an altered hepatocyte ultrastructure. In addition, CCl4-induced acute hepatotoxicity was associated with an increase in hepatic tumor necrosis factor-α (TNF-α) and α-smooth muscle actin (α-SMA) protein expression, which was significantly decreased in the livers of mice pre-treated with chrysin (P<0.001), similar to the results of the silymarin pre-treated group (P<0.001). Treatment with chrysin prior to CCl4 exposure significantly reduced the activity of enzymes used as biochemical markers of poor liver function compared with the group which did not receive pre-treatment (P<0.001). In addition, the results of histopathological and electron microscopy liver examination showed chrysin pre-treatment reduced the effects of CCl4 treatment. Molecular modeling results demonstrated that the hepatoprotective activity of chrysin is mediated through TNF-α, as it reduces soluble TNF-α generation via blocking TNF-α-converting enzyme activity. In conclusion, the results of the present study suggest that inflammatory pathways are activated in CCl4-induced acute liver damage, which are ameliorated by chrysin pre-treatment. This indicates that chrysin is a potent hepatoprotective agent, similarly to silymarin at the same dose, which has the potential to be a viable alternative to conventional hepatoprotective treatments. D.A. Spandidos 2017-05 2017-03-02 /pmc/articles/PMC5443293/ /pubmed/28565752 http://dx.doi.org/10.3892/etm.2017.4181 Text en Copyright: © Hermenean et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Hermenean, Anca Mariasiu, Teodora Navarro-González, Inmaculada Vegara-Meseguer, Josefina Miuțescu, Eftimie Chakraborty, Sandipan Pérez-Sánchez, Horacio Hepatoprotective activity of chrysin is mediated through TNF-α in chemically-induced acute liver damage: An in vivo study and molecular modeling |
title | Hepatoprotective activity of chrysin is mediated through TNF-α in chemically-induced acute liver damage: An in vivo study and molecular modeling |
title_full | Hepatoprotective activity of chrysin is mediated through TNF-α in chemically-induced acute liver damage: An in vivo study and molecular modeling |
title_fullStr | Hepatoprotective activity of chrysin is mediated through TNF-α in chemically-induced acute liver damage: An in vivo study and molecular modeling |
title_full_unstemmed | Hepatoprotective activity of chrysin is mediated through TNF-α in chemically-induced acute liver damage: An in vivo study and molecular modeling |
title_short | Hepatoprotective activity of chrysin is mediated through TNF-α in chemically-induced acute liver damage: An in vivo study and molecular modeling |
title_sort | hepatoprotective activity of chrysin is mediated through tnf-α in chemically-induced acute liver damage: an in vivo study and molecular modeling |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443293/ https://www.ncbi.nlm.nih.gov/pubmed/28565752 http://dx.doi.org/10.3892/etm.2017.4181 |
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