A novel synthetic oleanolic acid derivative (CPU-II2) attenuates liver fibrosis in mice through regulating the function of hepatic stellate cells

被引：22

作者：

Wu, Li-Mei ^{[1
]}

Wu, Xing-Xin ^{[1
]}

Sun, Yang ^{[1
]}

Kong, Xiang-Wen ^{[2
]}

Zhang, Yi-Hua ^{[2
]}

Xu, Qiang ^{[1
]}

机构：

[1] Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China

[2] China Pharmaceut Univ, Ctr Drug Discovery, Nanjing 210009, Peoples R China

来源：

JOURNAL OF BIOMEDICAL SCIENCE | 2008年 / 15卷 / 02期

关键词：

CPU-II2; HSC-T6; cells; liver fibrosis; oleanolic acid derivative; p38; MAPK;

D O I：

10.1007/s11373-007-9216-9

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Regulation on the function of the hepatic stellate cells (HSCs) is one of the proposed therapeutic approaches to liver fibrosis. In the present study, we examined the in vitro and in vivo effects of CPU-II2, a novel synthetic oleanolic acid (OLA) derivative with nitrate, on hepatic fibrosis. This compound alleviated CCl4-induced hepatic fibrosis in mice with a decrease in hepatic hydroxyproline (Hyp) content and histological changes. CPU-II2 also attenuated the mRNA expression of alpha-smooth muscle actin (alpha-SMA) and tissue inhibitor of metalloproteinase type 1 (TIMP-1) induced by CCl4 in mice and reduced both mRNA and protein levels of alpha-SMA in HSC-T6 cells. Interestingly, CPU-II2 did not affect the survival of HSC-T6 cells but decreased the expression of procollagen-alpha 1 (I) in HSC-T6 cells through down-regulating the phosphorylation of p38 MAPK. Conclusion: CPU-II2 attenuates the development of liver fibrosis rather by regulating the function of HSCs through p38 MAPK pathway than by damaging the stellate cells.

引用

页码：251 / 259

页数：9

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