Quercetin Protects Mice from ConA-Induced Hepatitis by Inhibiting HMGB1-TLR Expression and Down-Regulating the Nuclear Factor Kappa B Pathway.
The dietary flavonoid quercetin has hepatoprotective effects. We analyzed the effects of quercetin on concanavalin A (ConA)-induced hepatitis in mice and its underlying molecular mechanisms of action. Mice were administered quercetin (50 mg/kg body weight, i.p.) or vehicle 30 min before intravenous administration of ConA. Quercetin pretreatment significantly reduced the ConA-induced elevations in plasma aminotransferase concentrations and liver necrosis, as well as reducing serum concentrations of the pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interferon-γ, and interleukin-4. Quercetin pretreatment also reduced expression of high-mobility group box 1 protein (HMGB1) and toll-like receptor (TLR)-2 and TLR-4 messenger RNA (mRNA) and protein in liver tissues. Quercetin pretreatment significantly inhibited degradation of inhibitory kappa B alpha and modulated ConA-induced nuclear translocation in the liver of nuclear factor kappa B (NF-κB) p65. These results demonstrate that quercetin protects against ConA-mediated hepatitis in mice by attenuating the HMGB1-TLRs-NF-κB signaling pathway.
Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.|Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, China.
Xi
X
Li
Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.|Shanghai Institute of Liver Diseases, 180 Fenglin Road, Shanghai, 200032, China.
Hong-Chun
HC
Liu
Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.|Shanghai Institute of Liver Diseases, 180 Fenglin Road, Shanghai, 200032, China.
Qun-Yan
QY
Yao
Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.|Shanghai Institute of Liver Diseases, 180 Fenglin Road, Shanghai, 200032, China.
Bei-Li
BL
Xu
Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.|Shanghai Institute of Liver Diseases, 180 Fenglin Road, Shanghai, 200032, China.
Shun-Cai
SC
Zhang
Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China. tu.chuantao@zs-hospital.sh.cn.|Shanghai Institute of Liver Diseases, 180 Fenglin Road, Shanghai, 200032, China. tu.chuantao@zs-hospital.sh.cn.
Chuan-Tao
CT
Tu
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D003208:Concanavalin A; D015536:Down-Regulation / Q000187:drug effects; D024243:HMGB1 Protein / Q000096:biosynthesis* / Q000235:genetics; D006505:Hepatitis / Q000188:drug therapy*; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis* / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000235:genetics; D000637:Transaminases / Q000097:blood; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D012333:RNA, Messenger; C498144:Rela protein, mouse; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D000072000:NF-KappaB Inhibitor alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D011794:Quercetin; D000637:Transaminases
hepatitis; high-mobility group box 1 protein; inflammation; nuclear factor κB; quercetin; toll-like receptor