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Silibinin Restores NAD+ Levels and Induces the SIRT1/AMPK Pathway in Non-Alcoholic Fatty Liver

Authors :
Federico Salomone
Ignazio Barbagallo
Justyna Godos
Vincenzo Lembo
Walter Currenti
Diana Cinà
Roberto Avola
Nicolantonio D’Orazio
Filomena Morisco
Fabio Galvano
Giovanni Li Volti
Source :
Nutrients, Vol 9, Iss 10, p 1086 (2017)
Publication Year :
2017
Publisher :
MDPI AG, 2017.

Abstract

Nicotinamide adenine dinucleotide (NAD+) homeostasis is emerging as a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and is tightly linked to the SIRT1/5’-AMP-activated protein kinase (AMPK) pathway. Silibinin, the main component of silymarin, has been proposed as a nutraceutical for the treatment of NAFLD. In this study, we aimed to identify whether silibinin may influence the NAD+/SIRT1 axis. To this end, C57BL/6 mice were fed a high fat diet (HFD) for 16 weeks, and were treated with silibinin or vehicle during the last 8 weeks. HepG2 cells were treated with 0.25 mM palmitate for 24 h with silibinin 25 µM or vehicle. HFD and palmitate administration led to oxidative stress, poly-(ADP-ribose)-polymerase (PARP) activation, NAD+ consumption, and lower SIRT1 activity. In mice fed the HFD, and in HepG2 treated with palmitate, we consistently observed lower levels of phospho-AMPKThr172 and phospho-acetyl-CoA carboxylaseSer79 and higher levels of nuclear sterol regulatory element-binding protein 1 activity, indicating de novo lipogenesis. Treatment of mice and HepG2 with silibinin abolished oxidative stress, and inhibited PARP activation thus restoring the NAD+ pool. In agreement with preserved NAD+ levels, SIRT1 activity and AMPK phosphorylation returned to control levels in mice and HepG2. Our results further indicate silibinin as a promising molecule for the treatment of NAFLD.

Details

Language :
English
ISSN :
20726643
Volume :
9
Issue :
10
Database :
Directory of Open Access Journals
Journal :
Nutrients
Publication Type :
Academic Journal
Accession number :
edsdoj.4a3af85819454505a37d0927f26fcd6c
Document Type :
article
Full Text :
https://doi.org/10.3390/nu9101086