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.