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Combination Treatment with Hydroxytyrosol and Vitamin E Improves NAFLD-Related Fibrosis
Non-alcoholic fatty liver disease (NAFLD)-related liver fibrosis results in the encapsulation of injured liver parenchyma by a collagenous scar mainly imputable to hepatic stellate cells’ activation. Approved pharmacological treatments against NAFLD-related fibrosis are still lacking, but natural co...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9505330/ https://www.ncbi.nlm.nih.gov/pubmed/36145170 http://dx.doi.org/10.3390/nu14183791 |
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author | Panera, Nadia Braghini, Maria Rita Crudele, Annalisa Smeriglio, Antonella Bianchi, Marzia Condorelli, Angelo Giuseppe Nobili, Rebecca Conti, Libenzio Adrian De Stefanis, Cristiano Lioci, Gessica Gurrado, Fabio Comparcola, Donatella Mosca, Antonella Sartorelli, Maria Rita Scoppola, Vittorio Svegliati-Baroni, Gianluca Trombetta, Domenico Alisi, Anna |
author_facet | Panera, Nadia Braghini, Maria Rita Crudele, Annalisa Smeriglio, Antonella Bianchi, Marzia Condorelli, Angelo Giuseppe Nobili, Rebecca Conti, Libenzio Adrian De Stefanis, Cristiano Lioci, Gessica Gurrado, Fabio Comparcola, Donatella Mosca, Antonella Sartorelli, Maria Rita Scoppola, Vittorio Svegliati-Baroni, Gianluca Trombetta, Domenico Alisi, Anna |
author_sort | Panera, Nadia |
collection | PubMed |
description | Non-alcoholic fatty liver disease (NAFLD)-related liver fibrosis results in the encapsulation of injured liver parenchyma by a collagenous scar mainly imputable to hepatic stellate cells’ activation. Approved pharmacological treatments against NAFLD-related fibrosis are still lacking, but natural compounds such as hydroxytyrosol (HXT) and vitamin E (VitE), are emerging as promising therapeutic opportunities. In this study, the potential anti-fibrotic effect of HXT + VitE combination therapy was investigated in vitro and in vivo. In particular, tumor growth factor (TGF)-β-activated LX-2 cells as an in vitro model, and carbon tetrachloride plus a Western diet as a mice model were employed. The effect of HXT + VitE on fibrosis was also investigated in children with biopsy-proven NAFLD. Our results demonstrated that HXT + VitE caused a reduction of proliferation, migration, contractility, and expression of pro-fibrogenic genes in TGF-β-activated LX-2 cells. HXT + VitE treatment also antagonized TGF-β-dependent upregulation of pro-oxidant NOX2 by interfering with nuclear translocation/activation of SMAD2/3 transcription factors. The mouse model of NAFLD-related fibrosis treated with HXT + VitE showed a marked reduction of fibrosis pattern by histology and gene expression. Accordingly, in children with NAFLD, HXT + VitE treatment caused a decrease of circulating levels of PIIINP and NOX2 that was supported over time. Our study suggests that HXT + VitE supplementation may improve NAFLD-related fibrosis. |
format | Online Article Text |
id | pubmed-9505330 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95053302022-09-24 Combination Treatment with Hydroxytyrosol and Vitamin E Improves NAFLD-Related Fibrosis Panera, Nadia Braghini, Maria Rita Crudele, Annalisa Smeriglio, Antonella Bianchi, Marzia Condorelli, Angelo Giuseppe Nobili, Rebecca Conti, Libenzio Adrian De Stefanis, Cristiano Lioci, Gessica Gurrado, Fabio Comparcola, Donatella Mosca, Antonella Sartorelli, Maria Rita Scoppola, Vittorio Svegliati-Baroni, Gianluca Trombetta, Domenico Alisi, Anna Nutrients Article Non-alcoholic fatty liver disease (NAFLD)-related liver fibrosis results in the encapsulation of injured liver parenchyma by a collagenous scar mainly imputable to hepatic stellate cells’ activation. Approved pharmacological treatments against NAFLD-related fibrosis are still lacking, but natural compounds such as hydroxytyrosol (HXT) and vitamin E (VitE), are emerging as promising therapeutic opportunities. In this study, the potential anti-fibrotic effect of HXT + VitE combination therapy was investigated in vitro and in vivo. In particular, tumor growth factor (TGF)-β-activated LX-2 cells as an in vitro model, and carbon tetrachloride plus a Western diet as a mice model were employed. The effect of HXT + VitE on fibrosis was also investigated in children with biopsy-proven NAFLD. Our results demonstrated that HXT + VitE caused a reduction of proliferation, migration, contractility, and expression of pro-fibrogenic genes in TGF-β-activated LX-2 cells. HXT + VitE treatment also antagonized TGF-β-dependent upregulation of pro-oxidant NOX2 by interfering with nuclear translocation/activation of SMAD2/3 transcription factors. The mouse model of NAFLD-related fibrosis treated with HXT + VitE showed a marked reduction of fibrosis pattern by histology and gene expression. Accordingly, in children with NAFLD, HXT + VitE treatment caused a decrease of circulating levels of PIIINP and NOX2 that was supported over time. Our study suggests that HXT + VitE supplementation may improve NAFLD-related fibrosis. MDPI 2022-09-14 /pmc/articles/PMC9505330/ /pubmed/36145170 http://dx.doi.org/10.3390/nu14183791 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Panera, Nadia Braghini, Maria Rita Crudele, Annalisa Smeriglio, Antonella Bianchi, Marzia Condorelli, Angelo Giuseppe Nobili, Rebecca Conti, Libenzio Adrian De Stefanis, Cristiano Lioci, Gessica Gurrado, Fabio Comparcola, Donatella Mosca, Antonella Sartorelli, Maria Rita Scoppola, Vittorio Svegliati-Baroni, Gianluca Trombetta, Domenico Alisi, Anna Combination Treatment with Hydroxytyrosol and Vitamin E Improves NAFLD-Related Fibrosis |
title | Combination Treatment with Hydroxytyrosol and Vitamin E Improves NAFLD-Related Fibrosis |
title_full | Combination Treatment with Hydroxytyrosol and Vitamin E Improves NAFLD-Related Fibrosis |
title_fullStr | Combination Treatment with Hydroxytyrosol and Vitamin E Improves NAFLD-Related Fibrosis |
title_full_unstemmed | Combination Treatment with Hydroxytyrosol and Vitamin E Improves NAFLD-Related Fibrosis |
title_short | Combination Treatment with Hydroxytyrosol and Vitamin E Improves NAFLD-Related Fibrosis |
title_sort | combination treatment with hydroxytyrosol and vitamin e improves nafld-related fibrosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9505330/ https://www.ncbi.nlm.nih.gov/pubmed/36145170 http://dx.doi.org/10.3390/nu14183791 |
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