Protective effects of curcumin against hepatic fibrosis induced by carbon tetrachloride: modulation of high-mobility group box 1, Toll-like receptor 4 and 2 expression.
The aim of the study was to investigate the effect of curcumin on the liver fibrosis induced by carbon tetrachloride (CCl(4)) in rats, and to elucidate its underlying molecular mechanisms. Rats were administered with CCl(4) together with or without curcumin for 6 weeks. Hepatic damage was evaluated by analysis of liver function tests in serum. Hepatic histopathology and collagen content were employed to quantify liver fibrosis; and activated hepatic stellate cells were assessed. Moreover, the mRNA and protein expression levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, high-mobility group box 1 (HMGB1), Toll like receptor (TLR) 2 and TLR4 were determined by quantitative real time PCR, Western blot or immunohistochemistry. Treatment with curcumin significantly attenuated CCl(4)-induce liver injury, hepatic inflammation and reduced the levels of proinflammatory mediators (TNF-α, IL-6 and MCP-1). Moreover, curcumin significantly inhibited extracellular matrix deposition, reduced the number of activated stellate cells, and decreased the levels of HMGB1, TLR4 and TLR2 expression in the rat model of fibrogenesis. These results suggest that curcumin could be an effective agent for preventing liver fibrosis and its mechanism may in part be a consequence of the reduction TLR2, TLR4 and HMGB1 expression.
Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, People's Republic of China. tuchuantao@hotmail.com
Chuan-tao
CT
Tu
Qun-yan
QY
Yao
Bei-li
BL
Xu
Ji-yao
JY
Wang
Chao-hui
CH
Zhou
Shun-cai
SC
Zhang
D000818:Animals; D001483:Base Sequence; D002251:Carbon Tetrachloride / Q000633:toxicity*; D003474:Curcumin / Q000627:therapeutic use*; D017931:DNA Primers; D024243:HMGB1 Protein / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D017931:DNA Primers; D024243:HMGB1 Protein; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D002251:Carbon Tetrachloride; D003474:Curcumin