Platycodi Radix attenuates dimethylnitrosamine-induced liver fibrosis in rats by inducing Nrf2-mediated antioxidant enzymes

被引:28
作者
Choi, Jae Ho [1 ]
Jin, Sun Woo [1 ]
Kim, Hyung Gyun [1 ]
Khanal, Tilak [1 ]
Hwang, Yong Pil [1 ,2 ]
Lee, Kyung Jin [3 ]
Choi, Chul Yung [4 ]
Chung, Young Chul [5 ]
Lee, Young Chun [5 ,6 ]
Jeong, Hye Gwang [1 ]
机构
[1] Chungnam Natl Univ, Coll Pharm, Dept Toxicol, Taejon, South Korea
[2] Int Univ Korea, Dept Pharmaceut Engn, Jinju, South Korea
[3] Asan Med Ctr, Asan Inst Life Sci, Seoul, South Korea
[4] Jeollanamdo Inst Nat Resources Res, Jeollanamdo, South Korea
[5] Int Univ Korea, Dept Food Sci, Jinju, South Korea
[6] Jangsaeng Doraji Co Ltd, Jinju, South Korea
基金
新加坡国家研究基金会;
关键词
Platycodi Radix; Liver fibrosis; Antioxidant enzymes; Nrf2; COX-2; TRANSCRIPTION FACTOR NRF2; HEPATIC-FIBROSIS; OXIDATIVE STRESS; AQUEOUS EXTRACT; NUCLEAR TRANSLOCATION; STELLATE CELL; GRANDIFLORUM; ACTIVATION; EXPRESSION; INDUCTION;
D O I
10.1016/j.fct.2013.02.033
中图分类号
TS2 [食品工业];
学科分类号
100403 [营养与食品卫生学];
摘要
The purpose of this study was to investigate the anti-fibrotic effects of the aqueous extract of the Platycodi Radix root (Changkil: CK) on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. DMN treatment for 4 weeks led to marked liver fibrosis as assessed by serum biochemistry, histopathological examination, and hepatic lipid peroxidation and collagen content. CK significantly inhibited DMN-induced increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, fibrosis score, and hepatic malondialdehyde and collagen content. CK also inhibited DMN-induced reductions in rat body and liver weights. Reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses revealed that CK inhibited DMN-induced increases in matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and tumor necrosis factor-alpha (TNF-alpha) mRNA, and collagen type I and alpha-smooth muscle actin protein. DMN-induced cyclooxygenase-2 (COX-2) expression and nuclear factor-kappa B (NF-kappa B) activation was reduced by CK treatment. Furthermore, CK induced activation of nuclear erythroid 2-related factor 2 (Nrf2)-mediated antioxidant enzymes such as gamma-glutamylcysteine synthetase (gamma-GCS), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and glutathione-S-transferase (GST) in HepG2 cells. These results demonstrated that CK attenuates DMN-induced liver fibrosis through the activation of Nrf2-mediated antioxidant enzymes. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码:231 / 239
页数:9
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