Flavonoids from Citrus aurantium ameliorate TNBS-induced ulcerative colitis through protecting colonic mucus layer integrity

Abstract

Intestinal barrier injury is recognized as the main reason for ulcerative colitis (UC) which is a chronic inflammatory disease and the effective therapeutic methods remain limited. In this study, we explored the protection effects of naringenin, nobiletin and hesperetin from Citrus aurantium on colonic mucus layer integrity. The UC mice model was induced by trinitrobenzenesulfonic acid (TNBS). Forty mg/kg/day of naringenin, nobiletin and hesperetin were administrated orally for 7 and 3 days before and after TNBS treatment. Then body weight, disease activity index (DAI) score and colon length were recorded. Colons were collected for immunofluorescence, RT-PCR and western blot assay. Lipopolysaccharide (LPS)-induced cell-co-culture system of Caco-2 and RAW264.7 cells were used to determine activities on protecting intestinal epithelial monolayers damage. Our results showed that Naringenin, nobiletin and hesperetin alleviated body weight loss and colon shortness, decreased DAI score, and up-regulated claudin-2, occludin and zona occludens-1 (ZO-1) expression significantly. Meanwhile, the flavonoids enhanced trans epithelial electric resistance, decreased the permeability and up-regulated occludin and ZO-1 expression in LPS-damaged epithelial monolayers system. Hence, Naringnien, nobiletin and hesperetin show the regulatory effect on UC by protecting colonic mucosa layer integrity. It is suggested the flavonoids may be new supplements for the treatment of UC.

Keywords: Colonic mucosa barrier; Hesperetin; Naringenin; Nobiletin; Ulcerative colitis.