title: Protective effect of ellagic acid on concanavalin A-induced hepatitis via toll-like receptor and mitogen-activated protein kinase/nuclear factor κB signaling pathways.
abstract: Ellagic acid (EA) is present in certain fruits and nuts, including raspberries, pomegranates, and walnuts, and has anti-inflammatory and antioxidant properties. The aims of this study were to examine the protective effect of EA on concanavalin A (Con A)-induced hepatitis and to elucidate its underlying molecular mechanisms in mice. Mice were orally administered EA at different doses before the intravenous delivery of Con A; the different experimental groups were as follows: (i) vehicle control, (ii) Con A alone without EA, (iii) EA at 50 mg/kg, (iv) EA at 100 mg/kg, and (v) EA at 200 mg/kg. We found that EA pretreatment significantly reduced the levels of plasma aminotransferase and liver necrosis in Con A-induced hepatitis. Also, EA significantly decreased the expression levels of the toll-like receptor 2 (TLR2) and TLR4 mRNA and protein in liver tissues. Further, EA decreased the phosphorylation of JNK, ERK1/2, and p38. EA-treated groups showed suppressions of nuclear factor κB (NF-κB) and IκB-α degradation levels in liver tissues. In addition, EA pretreatment decreased the expression of pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β). These results suggest that EA protects against T-cell-mediated hepatitis through TLR and mitogen-activated protein kinase (MAPK)/NF-κB signaling pathways.
authors.affiliation: Department of Environmental and Health Chemistry, College of Pharmacy, Chung-Ang University , 221 Huksuk-Dong, Dongjak-Ku, Seoul 156-756, South Korea.
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Lee
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Won
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Choi
authors.forename: Hye Hyeon
authors.initials: HH
authors.lastname: Cha
authors.forename: Yeo Jin
authors.initials: YJ
authors.lastname: Jang
authors.forename: Seohyeon
authors.initials: S
authors.lastname: Park
authors.forename: Han Gyeol
authors.initials: HG
authors.lastname: Kim
authors.forename: Hyung Chul
authors.initials: HC
authors.lastname: Kim
authors.forename: Dae Kyong
authors.initials: DK
authors.lastname: Kim
mesh_terms: D000818:Animals; D003208:Concanavalin A / Q000009:adverse effects; D004610:Ellagic Acid / Q000008:administration & dosage*; D006505:Hepatitis / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D020011:Protective Agents; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D003208:Concanavalin A; D004610:Ellagic Acid; D020928:Mitogen-Activated Protein Kinases
keywords: concanavalin A; ellagic acid; hepatitis; mitogen-activated protein kinase; nuclear factor κB; toll-like receptors