期刊
IUBMB LIFE
卷 67, 期 4, 页码 312-321出版社
WILEY
DOI: 10.1002/iub.1348
关键词
tetramethylpyrazine; liver fibrosis; NLRP3 inflammasome; inflammation; hepatic stellate cells
资金
- National Natural Science Foundation of China [81270514, 30873424]
- Doctoral Discipline Foundation of Ministry of Education of China [20103237110010]
- Project for Supporting Jiangsu Provincial Talents in Six Fields [2009-B-010]
- Eleven-Five National Science and Technology Supporting Program [2008BAI51B02]
Hepatic fibrosis is concomitant with liver inflammation, which has been highlighted as significant treatment of chronic liver disease. We previously demonstrated that tetramethylpyrazine (TMP), the effective component of Ligusticum chuanxiong Hort, can inhibit the activation of HSCs and consequential anti-hepatic fibrosis. In this study, our work demonstrated that TMP improved liver histological architecture, decreased hepatic enzyme levels and attenuated collagen deposition in the rat fibrotic liver. In addition, TMP significantly protected the liver from CCl4-caused injury and fibrogenesis by suppressing inflammation with reducing levels of inflammatory cytokines, including tumor necrosis factor- (TNF-), NLRP3, nuclear factor-kappa B (NF-B) and interleukin-1 (IL-1). Experiments in vitro showed that TMP inhibited inflammatory cytokine expression in HSCs associated with disrupting platelet-derived growth factor-b receptor (PDGF-R)/NLRP3/caspase1 pathway. These data collectively indicate that TMP can attenuate liver inflammation in liver fibrosis and possibly by targeting HSCs via PDGF-R/NLRP3/caspase1 pathway. It provides novel mechanistic insights into TMP as a potential therapeutic remedy for hepatic fibrosis. (c) 2015 IUBMB Life, 67(4):312-321, 2015
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