Catalposide, a compound isolated from catalpa ovata, attenuates induction of intestinal epithelial proinflammatory gene expression and reduces the severity of trinitrobenzene sulfonic Acid-induced colitis in mice.
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.
Kim
Sang-Wook
SW
Digestive Disease Research Institute, Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan, Chonbuk 570-749, Seoul 122-701, Korea.
Choi
Suck-Chei
SC
Choi
Eun-Young
EY
Kim
Kyoung-Suk
KS
Oh
Jae-Min
JM
Lee
Hyun-Ju
HJ
Oh
Hyun-Mee
HM
Kim
Soonhag
S
Oh
Berm-Seok
BS
Kimm
Ku-Chan
KC
Lee
Moo-Hyung
MH
Seo
Geom-Seog
GS
Kim
Tae-Hyeon
TH
Oh
Hyun-Cheol
HC
Woo
Won-Hong
WH
Kim
Youn-Seok
YS
Pae
Hyun-Ock
HO
Park
Do-Sim
DS
Chung
Hun-Taeg
HT
Jun
Chang-Duk
CD
D000818:Animals; D003092:Colitis / Q000188:drug therapy* / Q000235:genetics* / Q000662:veterinary; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D004195:Disease Models, Animal; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects*; D005960:Glucosides / Q000494:pharmacology*; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012720:Severity of Illness Index; D015398:Signal Transduction; D014301:Trinitrobenzenes / Q000008:administration & dosage
D016207:Cytokines; D005960:Glucosides; D014301:Trinitrobenzenes; C006928:catalposide