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Naringin Inhibits ROS ‐activated MAPK Pathway in High Glucose‐induced Injuries in H9c2 Cardiac Cells
Author(s) -
Chen Jingfu,
Guo Runmin,
Yan Hai,
Tian Lihong,
You Qiong,
Li Shanghai,
Huang Ruina,
Wu Keng
Publication year - 2014
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12153
Subject(s) - naringin , mapk/erk pathway , p38 mitogen activated protein kinases , viability assay , reactive oxygen species , apoptosis , pharmacology , chemistry , protein kinase a , kinase , microbiology and biotechnology , biochemistry , biology , chromatography
Naringin, an active flavonoid isolated from citrus fruit extracts, exhibits biological and pharmacological properties, such as antioxidant activity and antidiabetic effect. Mitogen‐activated protein kinase ( MAPK ) signalling pathway has been shown to participate in hyperglycaemia‐induced injury. The present study tested the hypothesis that naringin protects against high glucose ( HG )‐induced injuries by inhibiting MAPK pathway in H9c2 cardiac cells. To examine this, the cells were treated with 35 mM glucose ( HG ) for 24 hr to establish a HG ‐induced cardiomyocyte injury model. The cells were pre‐treated with 80 μM naringin for 2 hr before exposure to HG . The findings of this study showed that exposure of H 9c2 cells to HG for 24 hr markedly induced injuries, as evidenced by a decrease in cell viability, increases in apoptotic cells and reactive oxygen species ( ROS ) production, as well as dissipation of mitochondrial membrance potential ( MMP ). These injuries were significantly attenuated by the pre‐treatment of cells with either naringin or SB 203580 (a selective inhibitor of p38 MAPK ) or U 0126 (a selective inhibitor of extracellular signal regulated kinase 1/2, ERK 1/2) or SP 600125 (a selective inhibitor of c‐jun N ‐termanal kinase, JNK ) before exposure to HG , respectively. Furthermore, exposure of cells to HG increased the phosphorylation of p38 MAPK , ERK 1/2 and JNK . The increased activation of MAPK pathway was ameliorated by pre‐treatment with either naringin or N ‐acetyl‐ L ‐cysteine ( NAC ), a ROS scavenger, which also reduced HG ‐induced cytotoxicity and apoptosis, leading to increase in cell viability and decrease in apoptotic cells. In conclusion, our findings provide new evidence for the first time that naringin protects against HG ‐induced injuries by inhibiting the activation of MAPK (p38 MAPK , ERK 1/2 and JNK ) and oxidative stress in H 9c2 cells.