Format

Send to

Choose Destination
Toxicol Lett. 2016 Nov 2;261:1-12. doi: 10.1016/j.toxlet.2016.09.002. Epub 2016 Sep 4.

Quercetin attenuates the activation of hepatic stellate cells and liver fibrosis in mice through modulation of HMGB1-TLR2/4-NF-κB signaling pathways.

Author information

1
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.
2
Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai Institute of Liver Diseases, Shanghai, China. Electronic address: jin.qianwen@zs-hospital.sh.cn.
3
Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai Institute of Liver Diseases, Shanghai, China. Electronic address: yao.qunyan@zs-hospital.sh.cn.
4
Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai Institute of Liver Diseases, Shanghai, China. Electronic address: xu.beili@zs-hospital.sh.cn.
5
Laboratory Animal Center, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: li.zheng1@zs-hospital.sh.cn.
6
Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai Institute of Liver Diseases, Shanghai, China. Electronic address: tu.chuantao@zs-hospital.sh.cn.

Abstract

This 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.

KEYWORDS:

Hepatic stellate cells; High-mobility group box 1; Liver fibrosis; Nuclear factor kappa-B; Quercetin; Toll like receptors

PMID:
27601294
DOI:
10.1016/j.toxlet.2016.09.002
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center