title: 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.affiliation: Shanghai Key Laboratory of Formulated Chinese Medicines and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Dou
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.forename: Aning
authors.initials: A
authors.lastname: Sun
authors.forename: Eryun
authors.initials: E
authors.lastname: Zhang
authors.forename: Lili
authors.initials: L
authors.lastname: Ding
authors.forename: Subhajit
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wei
authors.forename: Guixin
authors.initials: G
authors.lastname: Chou
authors.forename: Zheng-Tao
authors.initials: ZT
authors.lastname: Wang
authors.forename: Sridhar
authors.initials: S
authors.lastname: Mani
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced* / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000494:pharmacology; D019587:Dietary Supplements; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D007249:Inflammation; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D044950:Flavanones; D005419:Flavonoids; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D016264:Dextran Sulfate; D008156:Luciferases; C005273:naringenin