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

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.

• Authors: Wei Dou, Jingjing Zhang, Aning Sun, Eryun Zhang, Lili Ding, Subhajit Mukherjee, Xiaohui Wei, Guixin Chou, Zheng-Tao Wang, Sridhar Mani
• Journal: The British journal of nutrition (Br J Nutr) Vol. 110 Issue 4 Pg. 599-608 (Aug 2013) ISSN: 1475-2662 [Electronic] England
• PMID: 23506745 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Flavanones
• Flavonoids
• NF-kappa B
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• Dextran Sulfate
• Luciferases
• naringenin

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Cell Line
• Colitis (chemically induced, prevention & control)
• Cytokines (metabolism)
• Dextran Sulfate (pharmacology)
• Dietary Supplements
• Female
• Flavanones (pharmacology)
• Flavonoids (pharmacology)
• Inflammation
• Luciferases (metabolism)
• Mice
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• Signal Transduction
• Toll-Like Receptor 4 (metabolism)