• Xi Li, Qianwen Jin, Qunyan Yao, Beili Xu, Zheng Li, and Chuantao Tu.
• Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai Institute of Liver Diseases, Shanghai, China; Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: li.xi@zs-hospital.sh.cn.
• Toxicol. Lett. 2016 Nov 2; 261: 1-12.

AbstractThis study aimed to investigate the effects of quercetin on liver fibrogenesis in mice and to elucidate the underlying molecular mechanisms. Mice were administered with carbon tetrachloride (CCl4) for eight weeks to induce liver fibrosis and concomitantly orally treated with quercetin (50mgkg-1day-1). Here, we demonstrated that quercetin dramatically ameliorated liver injury, inflammation, and hepatic fibrogenesis induced by CCl4. Quercetin also inhibited the activation of hepatic stellate cells (HSC) in vivo and in vitro, as evaluated by α-smooth muscle actin (α-SMA) expression, which is a specific marker of HSC activation. Moreover, reduced fibrosis was associated with decreased high-mobility group box 1 (HMGB1), toll like receptor (TLR) 2 and TLR4 genes, and protein expression. Quercetin also inhibited the cytoplasmic translocation of HMGB1 in hepatocytes of fibrotic livers. Further investigation demonstrated that quercetin treatment significantly attenuated CCl4-induced nuclear translocation of the nuclear factor-κB (NF-κB) p65 and inhibited degradation of IκBα (an inhibitor of NF-κB) expression in the liver compared with vehicle-treated fibrotic mice. Considered together, our data indicate that quercetin has hepatoprotective and anti-fibrotic effects in animal models of liver fibrosis, the mechanism of which may be involved in modulating the HMGB1-TLR2/4-NF-κB signaling pathways.Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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