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Mol Nutr Food Res. 2015 May;59(5):829-42. doi: 10.1002/mnfr.201400614. Epub 2015 Mar 16.

Citrus nobiletin ameliorates experimental colitis by reducing inflammation and restoring impaired intestinal barrier function.

Author information

1
Department of Pharmacology, Dalian Medical University, Dalian, P. R. China.

Abstract

SCOPE:

Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract. Citrus nobiletin can exert robust anti-inflammatory effects in vivo and in vitro. We evaluated the impact of nobiletin on the excessive inflammatory response and impaired barrier function in a rodent colitis model.

METHODS AND RESULTS:

Colitis was established by infusion with 1 mL 2,4,6-trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol (40% v/v) in rats at a 125 mg/kg dose. Caco-2 cell monolayer exposed to LPSs is used as a culture model for intestinal permeability measurements. Nobiletin decreased rat epithelial proinflammatory cytokines and mediators production. Nobiletin restored impaired barrier function in colitic rats and Caco-2 monolayer. Nobiletin decreased protein expressions of Akt, nuclear factor-kappa B (NF-κB), and myosin light chain kinase (MLCK) isolated from rat intestinal epithelial tissue and Caco-2 cell, respectively. PI3K inhibitor or siRNA targeting of either Akt or NF-κB mitigated the impact of nobiletin on MLCK expression and barrier function in Caco-2 monolayer, respectively.

CONCLUSION:

Nobiletin exerted anti-inflammatory effects in TNBS-induced colitis through the downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) expression. Nobiletin restored barrier function, which had been damaged after TNBS administration, through the inhibition of the Akt-NF-κB-MLCK pathway.

KEYWORDS:

Akt; Colitis; Impaired barrier function; NF-κB; Nobiletin

PMID:
25655748
DOI:
10.1002/mnfr.201400614
[Indexed for MEDLINE]

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