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. 2015 Sep;28(1):531-9.
doi: 10.1016/j.intimp.2015.06.036. Epub 2015 Jul 25.

Quercetin Protects Mouse Liver Against CCl₄-induced Inflammation by the TLR2/4 and MAPK/NF-κB Pathway

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Quercetin Protects Mouse Liver Against CCl₄-induced Inflammation by the TLR2/4 and MAPK/NF-κB Pathway

Jie-Qiong Ma et al. Int Immunopharmacol. .

Abstract

Quercetin (QE), a natural flavonoid, has many medical beneficial effects. However, its protective effects against carbon tetrachloride (CCl4) induced injury in liver have not been clarified. The aim of the present study is to illustrate the effects of QE on hepatic oxidative injury and inflammation in mice exposed to CCl4. ICR (Institute of Cancer Research) mice were exposed to CCl4 with or without QE co-administration for one week. Our results showed that QE administration significantly inhibited CCl4-induced liver injury. One of the potential mechanisms of QE action was decreasing the oxidative stress, which is consistent with decreasing of lipid peroxidation level and increasing the antioxidant enzyme activities in livers of mice. Furthermore, QE significantly decreased cytochrome P450 2E1 (CYP2E1) expression and production of pro-inflammatory markers such as inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2) and nitric oxide (NO) in livers of CCl4-treated mouse. In the process of exploring the underlying mechanisms of QE action, we found that QE significantly inhibited the Toll-like receptor 2 (TLR2) and the Toll-like receptor 4 (TLR4) activation and mitogen-activated protein kinase (MAPK) phosphorylation, which in turn inactivated NF-κB and the inflammatory cytokines in livers of the CCl4-treated mice. In conclusion, these results suggested that the inhibition of CCl4-induced inflammation by QE is due to its anti-oxidant activity and its ability to modulate the TLR2/TLR4 and MAPK/NF-κB signaling pathway.

Keywords: CCl(4); Inflammation; Liver; MAPK; Quercetin; TLR2/4.

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