Teupolioside, a phenylpropanoid glycosides of Ajuga reptans, biotechnologically produced by IRBN22 plant cell line, exerts beneficial effects on a rodent model of colitis.
The aim of the present study was to examine the effects of phenylpropanoid glycoside, teupolioside, biotechnologically produced by IRBN22 Ajuga reptans cell line, in rats subjected to experimental colitis. Colitis was induced in rats by intracolonic instillation of dinitrobenzene sulfonic acid (DNBS). Teupolioside was administered daily orally (0.2 or 2mgkg(-1)). On Day 4, animals were sacrificed and tissues were taken for histological and biochemical analysis. Four days after DNBS administration, colon TNF-alpha and IL-1beta productions were increased, associated with colon damage. Neutrophil infiltration, by myeloperoxidase activity, in the mucosa was associated with up-regulation of ICAM-1 and P-selectin and high levels of malondialdehyde. Immunohistochemistry for nitrotyrosine and poly (ADP-ribose) polymerase (PARP) showed an intense staining in the inflamed colon. Biochemical methods and zymography were used to analyze MMP-9 and -2 activities in colon tissues from DNBS-injured rats. Treatment with teupolioside significantly reduced the appearance of diarrhoea and the loss of body weight. This was associated with a remarkable amelioration in the disruption of the colonic architecture and a significant reduction in colonic myeloperoxidase activity and malondialdehyde levels. Teupolioside also reduced the pro-inflammatory cytokines release, the appearance of nitrotyrosine and PARP immunoreactivity in the colon and reduced the up-regulation of ICAM-1 and the expression of P-selectin. Therefore, teupolioside also reduced proMMP-9 and -2 activity induced in the colon by DNBS administration. The results of this study suggested that administration of teupolioside may be beneficial for treatment of inflammatory bowel disease.
Di Paola
Rosanna
R
IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy.
Esposito
Emanuela
E
Mazzon
Emanuela
E
Riccardi
Luisa
L
Caminiti
Rocco
R
Dal Toso
Roberto
R
Pressi
Giovanna
G
Cuzzocrea
Salvatore
S
D031328:Ajuga / Q000737:chemistry* / Q000166:cytology; D000818:Animals; D001557:Benzenesulfonates / Q000008:administration & dosage; D002109:Caffeic Acids / Q000302:isolation & purification / Q000627:therapeutic use*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000201:enzymology / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014312:Trisaccharides / Q000302:isolation & purification / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D001557:Benzenesulfonates; D002109:Caffeic Acids; D053583:Interleukin-1beta; D019007:P-Selectin; D017392:Thiobarbituric Acid Reactive Substances; D014312:Trisaccharides; D014409:Tumor Necrosis Factor-alpha; C007488:dinitrobenzenesulfonic acid; D018799:Intercellular Adhesion Molecule-1; C539158:teupolioside; D052247:Nitric Oxide Synthase Type II; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9