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Epigallocatechin gallate attenuates fibrosis, oxidative stress, and inflammation in non-alcoholic fatty liver disease rat model through TGF/SMAD, PI3 K/Akt/FoxO1, and NF-kappa B pathways

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Abstract

Purpose

To investigate the protective mechanisms of an 85 % pure extract of (−) epigallocatechin gallate (EGCG) in the development of fibrosis, oxidative stress and inflammation in a recently developed dietary-induced animal model of non-alcoholic fatty liver disease (NAFLD).

Methods

Female Sprague–Dawley rats were fed with either normal rat diet or high-fat diet for 8 weeks to develop NAFLD. For both treatments, rats were treated with or without EGCG (50 mg/kg, i.p. injection, 3 times per week). At the end, blood and liver tissue samples were obtained for histology, molecular, and biochemical analyses.

Results

Non-alcoholic fatty liver disease (NAFLD) rats showed significant amount of fatty infiltration, necrosis, fibrosis, and inflammation. This was accompanied by a significant expressional increase in markers for fibrosis, oxidative stress, and inflammation. TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways were also activated. Treatment with EGCG improved hepatic histology (decreased number of fatty score, necrosis, and inflammatory foci), reduced liver injury (from ~0.5 to ~0.3 of ALT/AST ratio), attenuated hepatic changes including fibrosis (reduction in Sirius Red and synaptophysin-positive stain) with down-regulation in the expressions of key pathological oxidative (e.g. nitrotyrosine formation) and pro-inflammatory markers (e.g. iNOS, COX-2, and TNF-α). EGCG treatment also counteracted the activity of TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways. Treatment with EGCG did not affect the healthy rats.

Conclusions

Epigallocatechin gallate (EGCG) reduced the severity of liver injury in an experimental model of NAFLD associated with lower concentration of pro-fibrogenic, oxidative stress, and pro-inflammatory mediators partly through modulating the activities of TGF/SMAD, PI3 K/Akt/FoxO1, and NF-κB pathways. Therefore, green tea polyphenols and EGCG are useful supplements in the prevention of NAFLD.

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Acknowledgments

We would like to thank Miss Carman Leung for her technical assistance in this project. This study was partly supported by the Small Project Funding of Research, University Research Committee, The University of Hong Kong, Hong Kong.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Center for Gene and Cell Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

    Jia Xiao

  2. Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L1-41, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China

    Chi Tat Ho, Emily C. Liong, Tung Ming Leung & George L. Tipoe

  3. Department of Physiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

    Man Lung Fung

  4. Research Centre of Heart, Brain, Hormone and Healthy Aging Centre, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

    Man Lung Fung & George L. Tipoe

  5. Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China

    Thomas Yue Huen Lau

  6. Department of Pathology and Laboratory Medicine, Dalhousie University School of Medicine, Halifax, NS, Canada

    Amin A. Nanji

  7. Liver Disease Division, Department of Medicine, Mount Sinai School of Medicine, New York City, NY, USA

    Tung Ming Leung

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  1. Jia Xiao
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  2. Chi Tat Ho
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Correspondence to Jia Xiao or George L. Tipoe.

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Jia Xiao and Chi Tat Ho have equally contributed to this work.

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Xiao, J., Ho, C.T., Liong, E.C. et al. Epigallocatechin gallate attenuates fibrosis, oxidative stress, and inflammation in non-alcoholic fatty liver disease rat model through TGF/SMAD, PI3 K/Akt/FoxO1, and NF-kappa B pathways. Eur J Nutr 53, 187–199 (2014). https://doi.org/10.1007/s00394-013-0516-8

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  • DOI: https://doi.org/10.1007/s00394-013-0516-8

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