- 作者: Li-Mei Wu; Xing-Xin Wu; Yang Sun; Xiang-Wen Kong; Yi-Hua Zhang; Qiang Xu
- 作者服務機構: 1 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing, 210093, China; ; 2 Center of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China
- 中文摘要: --
- 英文摘要: 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 α-smooth muscle actin (α-SMA) and tissue inhibitor of metalloproteinase type 1 (TIMP-1) induced by CCl4 in mice and reduced both mRNA and protein levels of α-SMA in HSC-T6 cells. Interestingly, CPU-II2 did not affect the survival of HSC-T6 cells but decreased the expression of procollagen-α1 (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.
- 中文關鍵字: --
- 英文關鍵字: CPU-II2, HSC-T6 cells, liver fibrosis, oleanolic acid derivative, p38 MAPK