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

Author(s): 
Koo, Yun-chang
Pyo, Min Cheol
Nam, Mi-Hyun
Hong, Chung-Oui
Yang, Sung-Yong
Lee, Kwang-Won
Item Type: 
Journal Article
Publication Title: 
Toxicology in vitro: an international journal published in association with BIBRA
Journal Abbreviation: 
Toxicol In Vitro
Publication Date: 
2016-08
Publication Year: 
2016
Pages: 
15-Aug
Volume: 
34
ISSN: 
1879-3177
DOI: 
10.1016/j.tiv.2016.03.013
Library Catalog: 
PubMed
Extra: 
PMID: 27021876

Turabian/Chicago Citation

Yun-chang Koo, Min Cheol Pyo, Mi-Hyun Nam, Chung-Oui Hong, Sung-Yong Yang and Kwang-Won Lee. 2016-08. "Chebulic acid prevents hepatic fibrosis induced by advanced glycation end-products in LX-2 cell by modulating Nrf2 translocation via ERK pathway." Toxicology in vitro: an international journal published in association with BIBRA 34: 15-Aug. 10.1016/j.tiv.2016.03.013.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1016/j.tiv.2016.03.013 | issn = 1879-3177 | volume = 34 | pages = 15-Aug | last = Koo | first = Yun-chang | coauthors = Pyo, Min Cheol, Nam, Mi-Hyun, Hong, Chung-Oui, Yang, Sung-Yong, Lee, Kwang-Won | title = Chebulic acid prevents hepatic fibrosis induced by advanced glycation end-products in LX-2 cell by modulating Nrf2 translocation via ERK pathway | journal = Toxicology in vitro: an international journal published in association with BIBRA | date = 2016-08 | pmid = | pmc = }} </ref>