Chebulic acid prevents hepatic fibrosis induced by advanced glycation end-products in LX-2 cell by modulating Nrf2 translocation via ERK pathway. (August 2016)

• Record Type: Journal Article
• Authors: Koo, Yun-Chang; Pyo, Min Cheol; Nam, Mi-Hyun; Hong, Chung-Oui; Yang, Sung-Yong; Lee, Kwang-Won
• Is Part Of: Toxicology in vitro. Volume 34(2016)
• Page Start: 8
• Page End: 15
• Publication Date: 2016-08
• Subjects: T. chebula Terminalia chebula Retz. -- Glycer-AGEs glyceraldehyde-derived advanced glycation end-products -- NASH nonalcoholic steatohepatitis -- ROS reactive oxygen species -- ARE antioxidant response element -- Nrf2 nuclear factor E2-related factor 2 -- MAP kinases mitogen-activated protein kinases -- ERK extracellular signal-regulated kinase -- HSCs hepatic stellate cells -- ECM extracellular matrix -- GCS γ-glutamylcysteine synthetase -- GCLC catalytic subunit of γ-glutamylcysteine synthetase -- HO-1 hemeoxygenase 1 -- NQO1 NAD(P)H:quinone reductase -- Sesn2 sestrin2; Chebulic acid -- Human hepatic stellate cell -- Advanced glycation end-product -- Hepatic fibrosis -- Nuclear factor E2-related factor; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2016.03.013
• Languages: English
• ISSNs: 0887-2333

Abstract

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. Highlights: Effects of glycer-AGEs on hepatic stellate cell line, LX-2 are investigated. Chebulic acid activates ERK-phosphorylation-mediated Nrf2 nuclear translocation. The Nrf translocation causes up-regulation of antioxidant protein production in LX-2. Chebulic acid inhibits formation of ROS and collagen proteins by glycer-AGEs in LX-2.