期刊
NUTRIENTS
卷 14, 期 18, 页码 -出版社
MDPI
DOI: 10.3390/nu14183791
关键词
NAFLD; fibrosis; antioxidants; PIIINP; NOX2
资金
- Italian Ministry of Health
- Fondazione Veronesi 2021 fellowship program
This study investigated the potential anti-fibrotic effect of HXT + VitE combination therapy on NAFLD-related fibrosis. The results demonstrated that HXT + VitE treatment reduced proliferation, migration, and contraction of fibrosis cells, decreased expression of pro-fibrogenic genes, and antagonized the pro-fibrotic effects by interfering with transcription factor translocation/activation. In mouse and pediatric NAFLD models, HXT + VitE treatment showed a reduction in 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 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)-beta-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-beta-activated LX-2 cells. HXT + VitE treatment also antagonized TGF-beta-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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