Protective Effect of Ellagic Acid on Concanavalin A‑Induced Hepatitis via Toll-Like Receptor and Mitogen-Activated Protein Kinase/Nuclear Factor κB Signaling Pathways

• Published in: Journal of agricultural and food chemistry Vol. 62; no. 41; pp. 10110 - 10117
• Main Authors: Lee, Jae Hong, Won, Jong Hoon, Choi, Jong Min, Cha, Hye Hyeon, Jang, Yeo Jin, Park, Seohyeon, Kim, Han Gyeol, Kim, Hyung Chul, Kim, Dae Kyong
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 15.10.2014; American Chemical Society, Books and Journals Division
• Subjects: Animals; antioxidant activity; concanavalin A; Concanavalin A - adverse effects; ellagic acid; Ellagic Acid - administration & dosage; fruits; hepatitis; Hepatitis - drug therapy; Hepatitis - etiology; Humans; interleukin-1beta; interleukin-6; intravenous injection; liver; liver protein; Male; messenger RNA; Mice; Mice, Inbred BALB C; mitogen-activated protein kinase; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; necrosis; NF-kappa B - genetics; NF-kappa B - metabolism; oral administration; phosphorylation; Phosphorylation - drug effects; pomegranates; Protective Agents - administration & dosage; protective effect; raspberries; signal transduction; Signal Transduction - drug effects; tissues; Toll-like receptor 2; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 2 - metabolism; Toll-like receptor 4; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; transcription factor NF-kappa B; tumor necrosis factor-alpha; walnuts; mitogen-activated protein kinase; nuclear factor κB; ellagic acid; toll-like receptors; hepatitis; concanavalin A
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf503188c

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.