期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 292, 期 -, 页码 19-29出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2015.12.024
关键词
Dioscin; Hepatic fibrosis; Nrf2; Oxidative stress; p38 MAPK; Sirt1
资金
- National Natural Science Foundation of China [81274195]
- Program for Liaoning Innovative Research Team in University [LT2013019]
- Liaoning BaiQianWan Talents Program [2015-65]
Oxidative stress is involved in hepatic stellate cells (HSCs) activation and extracellular matrix overproduction. We previously reported the promising effects of dioscin against CCl4-induced liver fibrosis, but its effects and mechanisms on BDL- and DMN-induced liver fibrosis remain unknown. The results in the present study indicated that dioscin significantly inhibited HSCs activation and attenuated hepatic fibrosis in rats. Furthermore, dioscin markedly up-regulated the levels of sirtuin 1 (Sirtl), HO-1, GST, GCLC and GCLM via increasing the nuclear trans location of nuclear erythroid factor 2-related factor 2 (Nrf2), which in turn inhibited mitogen-activated protein kinase 14 (p38 MAPK) phosphorylation and reduced the levels of COL1A1, COL3A1, alpha-SMA and fibronectin. These results were further validated by knockdown of Sirtl and Nrf2 using siRNAs silencing, and abrogation of p38 MAPK using SB-203580 (a p38 MAPK inhibitor) in HSC-T6 and LX-2 cells. Collectively, our findings confirmed the potent effects of dioscin against liver fibrosis and also provided novel insights into the mechanisms of this compound as a candidate for the prevention of liver fibrosis in the future. (C) 2015 Elsevier Inc. All rights reserved.
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