期刊
BRITISH JOURNAL OF NUTRITION
卷 110, 期 4, 页码 599-608出版社
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S0007114512005594
关键词
Dextran sulphate sodium-induced colitis; Toll-like receptor 4: NF-kappa B; Signalling pathways; Naringenin
资金
- National Natural Science Foundation of China [81150040, U1032604]
- Natural Science Foundation of Shanghai [12ZR1431400]
- National Institutes of Health [RO1CA127231]
- Damon Runyon Foundation Clinical Investigator Award [CI 1502]
- Albert Einstein College of Medicine
Naringenin, one of the most abundant flavonoids in citrus, grapefruits and tomatoes, has been used as a traditional anti-inflammatory agent for centuries. However, the molecular mechanism of naringenin in intestinal inflammation remains unknown so far. The present study investigated a molecular basis for the protective effect of naringenin in dextran sulphate sodium-induced murine colitis. Pre-administration of naringenin significantly reduced the severity of colitis and resulted in down-regulation of pro-inflammatory mediators (inducible NO synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), cyclo-oxygenase-2 (Cox2), TNF-alpha and IL-6 mRNA) in the colon mucosa. The decline in the production of pro-inflammatory cytokines, specifically TNF-alpha and IL-6, correlated with a decrease in mucosal Toll-like receptor 4 (TLR4) mRNA and protein. Phospho-NF-kappa B p65 protein was significantly decreased, which correlated with a similar decrease in phospho-I kappa B alpha protein. Consistent with the in vivo results, naringenin exposure blocked lipopolysaccharide-stimulated nuclear translocation of NF-kappa B p65 in mouse macrophage RAW264.7 cells. In addition, in vitro NF-kappa B reporter assays performed on human colonic HT-29 cells exposed to naringenin demonstrated a significant inhibition of TNF-alpha-induced NF-kappa B luciferase expression. Thus, for the first time, the present study indicates that targeted inhibition of the TLR4/NF-kappa B signalling pathway might be an important mechanism for naringenin in abrogating experimental colitis.
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