The anti-fibrotic effects of epigallocatechin-3-gallate in bile duct-ligated cholestatic rats and human hepatic stellate LX-2 cells are mediated by the PI3K/Akt/Smad pathway

被引：59

作者：

Yu, Dong-ke ^{[1
,2
,3
,4
]}

Zhang, Cai-xia ^{[1
,2
]}

Zhao, Shuang-shuang ^{[1
,2
]}

Zhang, Sheng-hua ^{[1
,2
]}

Zhang, Hao ^{[1
,2
]}

Cai, Shi-ying ^{[5
,6
]}

Shao, Rong-guang ^{[1
,2
]}

He, Hong-wei ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China

[2] Peking Union Med Coll, Beijing 100050, Peoples R China

[3] Sichuan Acad Med Sci, Chengdu 610072, Peoples R China

[4] Sichuan Prov Peoples Hosp, Chengdu 610072, Peoples R China

[5] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA

[6] Yale Univ, Sch Med, Ctr Liver, New Haven, CT 06520 USA

来源：

ACTA PHARMACOLOGICA SINICA | 2015年 / 36卷 / 04期

基金：

中国国家自然科学基金;

关键词：

epigallocatechin-3-gallate; liver fibrosis; cholestasis; bile duct-ligated rats; hepatic stellate cells; TGF-beta; 1; PI3K/Akt/Smad pathway; G3BP1; LY294002; GREEN-TEA POLYPHENOL; LIVER-DISEASE; OXIDATIVE STRESS; FIBROSIS; SUPPRESSES; GROWTH; PATHOGENESIS; INFLAMMATION; EXPRESSION; MICE;

D O I：

10.1038/aps.2014.155

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Aim: (-)-Epigallocatechin-3-gallate (EGCG) is one of the most abundant polyphenols in green tea with strong antioxidant activity and various therapeutic effects. In this study, we investigated the anti-fibrotic effects of EGCG and underlying mechanisms in bile ductligated (BDL) rats and a liver fibrosis model in vitro. Methods: BDL rats were treated with EGCG (25 mg.kg(-1).d(-1), po) for 14 d, and then the serum, bile and liver samples were collected. Liver fibrosis was assessed by serum, urine and bile biochemistry analyses and morphological studies of liver tissues. TGF-beta 1-stimulated human hepatic stellate LX-2 cells were used as a liver fibrosis model in vitro. The expression of liver fibrogenic genes and signaling proteins in the PI3K/Akt/Smad pathway was examined using Western blotting and/or real-time PCR. Results: In BDL rats, EGCG treatment significantly ameliorates liver necrosis, inflammation and fibrosis, and suppressed expression of the genes associated with liver inflammation and fibrogenesis, including TNF-alpha, IL-1 beta, TGF-beta 1, MMP-9, alpha-SMA, and COL1A1. In LX-2 cells, application of EGCG (10, 25 mu mol/L) dose-dependently suppressed TGF-beta 1-stimulated expression of COL1A1, MMP-2, MMP-9, TGF-beta 1, TIMP1, and alpha-SMA. Furthermore, EGCG significantly suppressed the phosphorylation of Smad2/3 and Akt in the livers of BDL rats and in TGF-beta 1-stimulated LX-2 cells. Application of LY294002, a specific inhibitor of PI3K, produced similar effects as EGCG did in TGF-beta 1-stimulated LX-2 cells, but co-application of EGCG and LY294002 did not produce additive effects. Conclusion: EGCG exerts anti-fibrotic effects in BDL rats and TGF-beta 1-stimulated LX-2 cells in vitro via inhibiting the PI3K/Akt/Smad pathway.

引用

页码：473 / 482

页数：10

共 20 条

[1] Lithocholic acid feeding induces segmental bile duct obstruction and destructive cholangitis in mice [J].