title: Quercetin protects mouse liver against CCl₄-induced inflammation by the TLR2/4 and MAPK/NF-κB pathway.
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.
authors.affiliation: School of Chemistry and Pharmaceutical Engineering, Sichuan University of Science and Engineering; No. 180, Huixing Road, 643000 Zigong City, Sichuan Province, PR China. Electronic address: a1032042419@126.com.
authors.forename: Jie-Qiong
authors.initials: JQ
authors.lastname: Ma
authors.affiliation: School of Chemistry and Pharmaceutical Engineering, Sichuan University of Science and Engineering; No. 180, Huixing Road, 643000 Zigong City, Sichuan Province, PR China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Chemistry and Pharmaceutical Engineering, Sichuan University of Science and Engineering; No. 180, Huixing Road, 643000 Zigong City, Sichuan Province, PR China.
authors.forename: Wan-Ru
authors.initials: WR
authors.lastname: Xie
authors.affiliation: School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tangshan New Area, 221116 Xuzhou City, Jiangsu Province, PR China.
authors.forename: Chan-Min
authors.initials: CM
authors.lastname: Liu
authors.affiliation: School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tangshan New Area, 221116 Xuzhou City, Jiangsu Province, PR China.
authors.forename: Si-Si
authors.initials: SS
authors.lastname: Liu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology* / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide; D011794:Quercetin; D002251:Carbon Tetrachloride; D002374:Catalase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D020928:Mitogen-Activated Protein Kinases
keywords: CCl(4); Inflammation; Liver; MAPK; Quercetin; TLR2/4