Protective effect of naringenin against experimental colitis via suppression of Toll-like receptor 4/NF-κB signalling

Wei Dou, Jingjing Zhang, Aning Sun, Eryun Zhang, Lili Ding, Subhajit Mukherjee, Xiaohui Wei, Guixin Chou, Zheng Tao Wang, Sridhar Mani

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89 Scopus citations

Abstract

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-α and IL-6 mRNA) in the colon mucosa. The decline in the production of pro-inflammatory cytokines, specifically TNF-α and IL-6, correlated with a decrease in mucosal Toll-like receptor 4 (TLR4) mRNA and protein. Phospho-NF-κB p65 protein was significantly decreased, which correlated with a similar decrease in phospho-IκBα protein. Consistent with the in vivo results, naringenin exposure blocked lipopolysaccharide-stimulated nuclear translocation of NF-κB p65 in mouse macrophage RAW264.7 cells. In addition, in vitro NF-κB reporter assays performed on human colonic HT-29 cells exposed to naringenin demonstrated a significant inhibition of TNF-α-induced NF-κB luciferase expression. Thus, for the first time, the present study indicates that targeted inhibition of the TLR4/NF-κB signalling pathway might be an important mechanism for naringenin in abrogating experimental colitis.

Original languageEnglish (US)
Pages (from-to)599-608
Number of pages10
JournalBritish Journal of Nutrition
Volume110
Issue number4
DOIs
StatePublished - Aug 28 2013

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Keywords

  • Dextran sulphate sodium-induced colitis
  • NF-κB
  • Naringenin
  • Signalling pathways
  • Toll-like receptor 4

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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