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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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Detalles Bibliográficos
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
Descripción
Sumario: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.