title: Chlorogenic acid ameliorated concanavalin A-induced hepatitis by suppression of Toll-like receptor 4 signaling in mice.
abstract: Chlorogenic acid (CGA), one of the most abundant dietary polyphenolic compounds, has been reported to exhibit anti-inflammatory ability. However, the hepatoprotective effects and molecular mechanisms of CGA on concanavalin A (Con A)-induced hepatitis have not been explored. In the present study, we found that pretreatment with CGA dose-dependently inhibited the elevation of plasma aminotransferases and alleviated hepatic pathological damage as well as hepatocyte apoptosis in Con A-exposed mice. Additionally, CGA markedly suppressed the production of serum tumor necrosis factor (TNF)-α and interferon (IFN)-γ, alleviated the infiltration of hepatic macrophages, neutrophils, and activated CD4+T lymphocytes in Con A-primed mice. Moreover, CGA downregulated Con A-induced hepatic expression of adhesion molecules (ICAM-1, VCAM-1 and ELAM-1) mRNA and protein, and inhibited Con A-activated Toll-like receptor (TLR) 4 signal molecules including TLR4, p-IRAK1, p-IκB, and p-p38. Finally, our results also showed that CGA exhibited a therapeutic effect, which CGA posttreatment improved hepatic damage at 1, 3, and 6h after Con A. Taken together, these data suggested that CGA could effectively prevent mice from Con A-induced hepatitis, which might be through suppressing the activation of TLR4 signaling, downregulating the expression of adhesion molecules, and alleviating the infiltration and activation of hepatic leukocytes and the production of pro-inflammatory cytokines.
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yinglin
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Anatomy, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Gong
authors.affiliation: Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China. Electronic address: jywan@cqmu.edu.cn.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Wan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002448:Cell Adhesion; D002726:Chlorogenic Acid / Q000627:therapeutic use*; D003208:Concanavalin A / Q000276:immunology; D006520:Hepatitis, Animal / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects* / Q000276:immunology; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D002726:Chlorogenic Acid; D007371:Interferon-gamma
keywords: Adhesion molecules; Chlorogenic acid; Concanavalin A; Hepatitis; Leukocytes; Toll-like receptor 4