Combination Treatment with Hydroxytyrosol and Vitamin E Improves NAFLD-Related Fibrosis.
Nadia PaneraMaria Rita BraghiniAnnalisa CrudeleAntonella SmeriglioMarzia BianchiAngelo Giuseppe CondorelliRebecca NobiliLibenzio Adrian ContiCristiano De StefanisGessica LiociFabio GurradoDonatella ComparcolaAntonella MoscaMaria Rita SartorelliVittorio ScoppolaGianluca Svegliati-BaroniDomenico TrombettaAnna AlisiPublished in: Nutrients (2022)
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.
Keyphrases
- liver fibrosis
- combination therapy
- induced apoptosis
- gene expression
- growth factor
- transforming growth factor
- cell cycle arrest
- poor prognosis
- young adults
- signaling pathway
- cell proliferation
- type diabetes
- transcription factor
- anti inflammatory
- epithelial mesenchymal transition
- climate change
- metabolic syndrome
- drug induced
- ultrasound guided
- dna methylation
- liver injury
- systemic sclerosis
- mass spectrometry
- binding protein
- weight loss
- pi k akt
- genome wide identification