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

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

Authors: Li, Xi  Jin, Qianwen  Yao, Qunyan  Xu, Beili  Li, Zheng  Tu, Chuantao 
Citation: Li X, etal., Toxicol Lett. 2016 Nov 2;261:1-12. doi: 10.1016/j.toxlet.2016.09.002. Epub 2016 Sep 4.
RGD ID: 18182936
Pubmed: PMID:27601294   (View Abstract at PubMed)
DOI: DOI:10.1016/j.toxlet.2016.09.002   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Liver Cirrhosis treatmentISOTlr2 (Mus musculus)18182936; 18182936 RGD 
Experimental Liver Cirrhosis treatmentISOTlr4 (Mus musculus)18182936; 18182936 RGD 
Experimental Liver Cirrhosis treatmentIEP 18182936; 18182936 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tlr2  (toll-like receptor 2)
Tlr4  (toll-like receptor 4)

Genes (Mus musculus)
Tlr2  (toll-like receptor 2)
Tlr4  (toll-like receptor 4)

Genes (Homo sapiens)
TLR2  (toll like receptor 2)
TLR4  (toll like receptor 4)


Additional Information