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European Journal of Nutrition

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01-03-2021 | Original Contribution

S-allylmercaptocysteine improves nonalcoholic steatohepatitis by enhancing AHR/NRF2-mediated drug metabolising enzymes and reducing NF-κB/IκBα and NLRP3/6-mediated inflammation

Authors: Qian Yu, Yann-yin Lee, Zheng-yun Xia, Emily C. Liong, Jia Xiao, George L. Tipoe

Published in: European Journal of Nutrition | Issue 2/2021

Abstract

Purpose

To investigate the novel molecular mechanisms of the antioxidant and anti-inflammatory properties of S-allylmercaptocysteine (SAMC) based on a transcriptomic study in a nonalcoholic steatohepatitis (NASH) rat model

Methods

NASH was induced in Sprague–Dawley rats by feeding with a high fat diet (HFD) for 12 weeks. 200 mg/kg SAMC was fed by oral gavage for 4 weeks from 9 to 12 week.

Results

SAMC co-administration attenuated HFD-induced liver injury, including the increased serum ALT, hepatic oxidative stress and inflammation. Transcriptomic analysis revealed that SAMC dramatically induced the XRE- and ARE-driven drug metabolising enzymes (DMEs) including Akr7a3, Akr1b8, and Nqo1. The nuclear translocation of the upstream regulator of xenobiotics metabolism, AHR, and regulator of antioxidant responses, NRF2, were significantly increased by SAMC treatment. Furthermore, SAMC counteracted the effects of HFD on NF-κB/IκB and NLRP3/6 pathways with decreasing protein levels of ASC, cleaved caspase-1, IL-18, and IL-1β. These results were further verified in another mice NASH model induced by an MCD diet with SAMC co-administration.

Conclusion

We propose that SAMC triggers AHR/NRF2-mediated antioxidant responses which may further suppress the NLRP3/6 inflammasome pathway and NF-κB activation, contributing to the improvement of NASH.

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Title: S-allylmercaptocysteine improves nonalcoholic steatohepatitis by enhancing AHR/NRF2-mediated drug metabolising enzymes and reducing NF-κB/IκBα and NLRP3/6-mediated inflammation
Authors: Qian Yu
Yann-yin Lee
Zheng-yun Xia
Emily C. Liong
Jia Xiao
George L. Tipoe
Publication date: 01-03-2021
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nutrition / Issue 2/2021
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-020-02305-1

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