European Journal of Nutrition

, Volume 53, Issue 1, pp 187–199

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

  • Jia Xiao
  • Chi Tat Ho
  • Emily C. Liong
  • Amin A. Nanji
  • Tung Ming Leung
  • Thomas Yue Huen Lau
  • Man Lung Fung
  • George L. Tipoe
Original Contribution

DOI: 10.1007/s00394-013-0516-8

Cite this article as:
Xiao, J., Ho, C.T., Liong, E.C. et al. Eur J Nutr (2014) 53: 187. doi:10.1007/s00394-013-0516-8

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.

Keywords

EGCGNAFLDFibrosisOxidative stressInflammation

Supplementary material

394_2013_516_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 14 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Jia Xiao
    • 1
  • Chi Tat Ho
    • 2
  • Emily C. Liong
    • 2
  • Amin A. Nanji
    • 6
  • Tung Ming Leung
    • 2
    • 7
  • Thomas Yue Huen Lau
    • 5
  • Man Lung Fung
    • 3
    • 4
  • George L. Tipoe
    • 2
    • 4
  1. 1.Center for Gene and Cell Engineering, Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenChina
  2. 2.Department of Anatomy, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina
  3. 3.Department of Physiology, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina
  4. 4.Research Centre of Heart, Brain, Hormone and Healthy Aging Centre, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina
  5. 5.Department of Health Technology and Informatics, Faculty of Health and Social SciencesThe Hong Kong Polytechnic UniversityHong KongChina
  6. 6.Department of Pathology and Laboratory MedicineDalhousie University School of MedicineHalifaxCanada
  7. 7.Liver Disease Division, Department of MedicineMount Sinai School of MedicineNew York CityUSA