Rutin has intestinal antiinflammatory effects in the CD4+ CD62L+ T cell transfer model of colitis

Cristina Mascaraque, Carlos Aranda, Borja Ocón, María Jesús Monte, María Dolores Suárez, Antonio Zarzuelo, José Juan García Marín, Olga Martínez-Augustin, Fermín Sánchez De Medina

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

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 57 mg/kg/day, while no effect was noted with 28.5 mg/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 3 mg/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.

Original languageEnglish
Pages (from-to)48-57
Number of pages10
JournalPharmacological Research
Volume90
DOIs
StatePublished - 1 Dec 2014
Externally publishedYes

Keywords

  • CD4+ CD62L+ T cell transfer colitis
  • Epithelial transport
  • Flavonoid
  • Rutin

Fingerprint

Dive into the research topics of 'Rutin has intestinal antiinflammatory effects in the CD4+ CD62L+ T cell transfer model of colitis'. Together they form a unique fingerprint.

Cite this