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Inflamm Bowel Dis ; 10(5): 564-72, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15472516

RESUMO

Certain irinoid-producing plants have been used as herbal anti-inflammatory remedies. Here we evaluated whether catalposide (CATP), a single compound isolated from irinoid-producing plant Catalpa ovata, has a potential for preventing or ameliorating diseases characterized by mucosal inflammation. Preliminary microarray-based gene expression test revealed that CATP, which alone did not significantly affect expression of any of the >8,000 genes analyzed, attenuated the expression of tumor necrosis factor-alpha (TNF-alpha)-induced proinflammatory genes including interleukin-8 (IL-8) in human intestinal epithelial HT-29 cells. Down-regulation of IL-8 mRNA accumulation was also reflected by the decreased IL-8 secretion in CATP-treated HT-29 cells. The signal transduction study revealed that CATP significantly attenuates TNF-alpha-mediated p38 and extracellular signal-regulated kinase (ERK) phosphorylation. Further, CATP reduced NF-kappaB-mediated transcriptional activation as well as Ikappa-Balpha degradation. To establish the in vivo relevance of these findings, we examined whether CATP could affect intestinal inflammation in vivo using the mouse model of trinitrobenzene sulfonic acid (TNBS)-induced inflammatory colitis. Intrarectal administration of CATP dramatically reduced the weight loss, colonic damage, and mucosal ulceration that characterize TNBS colitis. Moreover, CATP suppressed the expression of TNF-alpha, interleukin-1beta, and intercellular adhesion molecule-1 along with the inhibition of NF-kappa B p65 translocation into nucleus in TNBS colitis. Collectively, current results demonstrate that CATP may be an effective agent for the treatment of diseases characterized by mucosal inflammation.


Assuntos
Colite/tratamento farmacológico , Colite/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Glucosídeos/farmacologia , Inflamação/genética , Animais , Colite/veterinária , Citocinas/análise , Citocinas/biossíntese , Modelos Animais de Doenças , Regulação para Baixo , Inflamação/patologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Índice de Gravidade de Doença , Transdução de Sinais , Trinitrobenzenos/administração & dosagem
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