Rutin, one of the most abundant
flavonoids in nature, has been shown to exert intestinal antiinflammatory effects in experimental models of
colitis. Our aim was to study the antiinflamatory effect of
rutin in the CD4+ CD62L+ T cell transfer model of
colitis, one of the closest to the human disease.
Colitis was induced by transfer of CD4+ CD62L+ T cells to Rag1(-/-) mice.
Rutin was administered by gavage as a postreatment. Treatment with
rutin improved
colitis at the dose of 57mg/kg/day, while no effect was noted with 28.5mg/kg/day. Therapeutic benefit was evidenced by a reduced disease activity index,
weight loss and damage score, plus a 36% lower colonic
myeloperoxidase and a 54% lower
alkaline phosphatase activity. In addition, a decreased secretion of proinflammatory
cytokines (IFNγ and TNFα) by mesenteric lymph node cells was observed ex vivo. The colonic expression of proinflammatory genes, including IFNγ, TNFα, CXCL1, S100A8 and IL-1β, was significantly reduced by more than 80% with
rutin as assessed by RT-qPCR.
Flavonoid treated mice exhibited decreased activation of splenic CD4+ cells (STAT4 phosphorylation and IFNγ expression) and reduced plasma
cytokine levels. This effect was also apparent in mucosal lymphocytes based on reduced STAT4 phosphorylation. The protective effect was comparable to that of 3mg/kg/day
budesonide.
Rutin had no effect on splenocytes or murine T cells in vitro, while its aglycone,
quercetin, exhibited a concentration dependent inhibition of proinflammatory
cytokines, including IFNγ.
Rutin but not
quercetin showed vectorial basolateral to apical transport in IEC18 cells, associated with reduced biotransformation. We conclude that
rutin exerts intestinal antiinflammatory activity in chronic, T lymphocyte dependent
colitis via
quercetin release and actions involving mucosal and lymph node T cells. Our results suggest that
rutin may be useful in the management of
inflammatory bowel disease in appropriate dosage conditions.