Chebulic acid prevents hepatic fibrosis induced by advanced glycation end-products in LX-2 cell by modulating Nrf2 translocation via ERK pathway

Yun Chang Koo, Min Cheol Pyo, Mi Hyun Nam, Chung Oui Hong, Sung Yong Yang, Kwang Won Lee

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Advanced glycation end-products (AGEs) are formed during normal aging, and at an accelerated rate in metabolic syndrome patients. Nonalcoholic steatohepatitis (NASH) can be caused by the AGEs in plasma, while glyceraldehyde-derived AGEs (glycer-AGEs) are significantly higher in the serum of NASH patients. In this study, we investigated the molecular mechanisms of chebulic acid, isolated from Terminalia chebula Retz., in the inhibition of glycer-AGEs induced production of reactive oxygen species (ROS) and collagen accumulation using the LX-2 cell line. Chebulic acid significantly inhibited the induction of ROS and accumulation of collagen proteins by glycer-AGEs. ERK phosphorylation and total nuclear factor E2-related factor 2 (Nrf2) protein expression were induced by chebulic acid in a dose-dependent manner. Chebulic acid was also found to induce translocation of Nrf2 into the nucleus, which was attenuated by inhibition of ERK phosphorylation through treatment with PD98059. Following translocation of Nrf2, chebulic acid induced the protein expressions of catalytic subunit of γ-glutamylcysteine synthetase and glutathione synthesis. Collagen accumulation was also significantly reduced by chebulic acid treatment. The observed effects of chebulic acid were all inhibited by PD98059 treatment. Taken together, these results suggest that chebulic acid prevents the glycer-AGEs-induced ROS formation of LX-2 cells and collagen accumulation by ERK-phosphorylation-mediated Nrf2 nuclear translocation, which causes upregulation of antioxidant protein production.

Original languageEnglish
Pages (from-to)8-15
Number of pages8
JournalToxicology in Vitro
Volume34
DOIs
Publication statusPublished - 2016 Aug 1

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NF-E2-Related Factor 2
Advanced Glycosylation End Products
MAP Kinase Signaling System
Fibrosis
Glyceraldehyde
Liver
Phosphorylation
Collagen
Reactive Oxygen Species
Proteins
Terminalia
Glutamate-Cysteine Ligase
chebulic acid
Glutathione
Catalytic Domain
Up-Regulation
Therapeutics
Antioxidants
Aging of materials
Cells

Keywords

  • Advanced glycation end-product
  • Chebulic acid
  • Hepatic fibrosis
  • Human hepatic stellate cell
  • Nuclear factor E2-related factor

ASJC Scopus subject areas

  • Toxicology

Cite this

Chebulic acid prevents hepatic fibrosis induced by advanced glycation end-products in LX-2 cell by modulating Nrf2 translocation via ERK pathway. / Koo, Yun Chang; Pyo, Min Cheol; Nam, Mi Hyun; Hong, Chung Oui; Yang, Sung Yong; Lee, Kwang Won.

In: Toxicology in Vitro, Vol. 34, 01.08.2016, p. 8-15.

Research output: Contribution to journalArticle

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