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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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