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.
Digestive Disease Research Institute, Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan, Chonbuk 570-749, Seoul 122-701, Korea.
Sang-Wook
SW
Kim
Suck-Chei
SC
Choi
Eun-Young
EY
Choi
Kyoung-Suk
KS
Kim
Jae-Min
JM
Oh
Hyun-Ju
HJ
Lee
Hyun-Mee
HM
Oh
Soonhag
S
Kim
Berm-Seok
BS
Oh
Ku-Chan
KC
Kimm
Moo-Hyung
MH
Lee
Geom-Seog
GS
Seo
Tae-Hyeon
TH
Kim
Hyun-Cheol
HC
Oh
Won-Hong
WH
Woo
Youn-Seok
YS
Kim
Hyun-Ock
HO
Pae
Do-Sim
DS
Park
Hun-Taeg
HT
Chung
Chang-Duk
CD
Jun
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