Chebulic acid prevents hepatic fibrosis induced by advanced glycation end-products in LX-2 cell by modulating Nrf2 translocation via ERK pathway
| Autor: | Chung Oui Hong, Sung Yong Yang, Yun Chang Koo, Kwang Won Lee, Min Cheol Pyo, Mi Hyun Nam |
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| Rok vydání: | 2016 |
| Předmět: |
Glycation End Products
Advanced Liver Cirrhosis 0301 basic medicine MAPK/ERK pathway Cell Survival MAP Kinase Signaling System NF-E2-Related Factor 2 Glutamate-Cysteine Ligase Cell Protective Agents Toxicology Collagen Type I Cell Line 03 medical and health sciences chemistry.chemical_compound Glycation medicine Humans Benzopyrans chemistry.chemical_classification Reactive oxygen species General Medicine Glutathione Chebulic acid Molecular biology Terminalia chebula 030104 developmental biology medicine.anatomical_structure Biochemistry chemistry Advanced glycation end-product Reactive Oxygen Species |
| Zdroj: | Toxicology in Vitro. 34:8-15 |
| ISSN: | 0887-2333 |
| DOI: | 10.1016/j.tiv.2016.03.013 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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