Intestinal barrier defects are involved in the pathogenesis of
inflammatory bowel disease. The present study investigated the ameliorative effects of
naringenin, a citrus
polyphenol, on intestinal tight junction (TJ) barrier defects and
inflammation in a murine model of
colitis. In Expt. 1, using a 2 × 2 fractional design, the mice were administered water or 2%
dextran sulfate sodium (DSS) in combination with feeding control or
naringenin-containing diets for 9 d (severe disease stage). DSS administration caused severe colon damage and
inflammation, as indicated by
body weight loss, increased clinical sores, colon shortening, and gene expressions of inflammatory
cytokines [
interferon-γ,
interleukin (IL)-6, macrophage inflammatory protein-2, and IL-17A). DSS administration also impaired TJ barrier integrity in the colon, as indicated by increased colon permeability and plasma
LPS-binding protein levels, resulting from the impaired colonic expression of TJ
proteins,
occludin,
junctional adhesion molecule-A, and
claudin-3. Supplemental feeding with
naringenin totally or partially attenuated these symptoms, suggesting that
naringenin ameliorates the DSS-induced
colitis at least partially through protection of the TJ barrier. In Expt. 2, analyses were performed at different disease stages (d 3, 6, and 9) to more widely examine the ameliorative role of
naringenin on the initiation and development of
colitis. DSS administration moderately induced colon shortening at d 3 and 6 and increased the disease activity index (DAI) and inflammatory
cytokine (IL-6 and IL-17A) expression without any significant increases in colonic permeability. Feeding
naringenin attenuated the increased DAI and colon shortening and tended to suppress the increased
cytokine expression. These findings suggest that the presence of an additional mechanism underlying the
naringenin-mediated, anticolitic effect along with barrier protection.