Subscribe to RSS
DOI: 10.1055/s-2004-818942
© Georg Thieme Verlag Stuttgart · New York
Intestinal Anti-Inflammatory Activity of Paepalantine, an Isocoumarin Isolated from the Capitula of Paepalanthus bromelioides, in the Trinitrobenzenesulphonic Acid Model of Rat Colitis
This study has been supported by grants from Instituto de Salud “Carlos III” (PI021732) and from Spanish Ministry of Science and Technology (SAF20002-02592). Research has been performed under the auspices of CYTED (Subprogram X, Project X.10 PIGASTRIN). Luiz C. Di Stasi was a fellowship of CNPq (PDE-200757/01-6)-BrazilPublication History
Received: July 23, 2003
Accepted: January 25, 2004
Publication Date:
19 April 2004 (online)
Abstract
The preventative intestinal anti-inflammatory activity of paepalantine, an isocoumarin isolated from the capitula of Paepalanthus bromelioides, was tested in the trinitrobenzenesulphonic acid (TNBS) model of rat colitis. This was performed in two different experimental settings, i. e. when the colonic mucosa is intact or when the mucosa is in process of recovery after an initial insult. The results obtained revealed that the paepalantine pretreatment, at doses of 5 and 10 mg/kg, significantly attenuated the colonic damage induced by TNBS in both situations, as it was evidenced both histologically and biochemically. This beneficial effect was associated with an improvement in the colonic oxidative status, since paepalantine prevented the glutathione depletion that occurred as a consequence of the colonic inflammation. In addition, the intestinal anti-inflammatory effect exerted by this isocoumarin was associated with an inhibition of colonic nitric oxide activity, which is upregulated as a consequence of the inflammatory process. In conclusion, the preventative effect exerted by paepalantine in the TNBS model of rat colitis is probably related with its antioxidant properties.
Abbreviations
AP:Alkaline phosphatase
IBD:Inflammatory bowel disease
GSH:Glutathione
MPO:Myeloperoxidase
NOS:Nitric oxide synthase
TNBS:Trinitrobenzenesulphonic acid
Key words
paepalantine - isocoumarin - capitula of Paepalanthus bromelioides - Eriocaulaceae - antioxidant activity - rat colitis - TNBS
References
- 1 Katz J A, Itoh J, Fiocchi C. Pathogenesis of inflammatory bowel disease. Curr Opin Gastroenterol. 1999; 15 291-7
- 2 Pavlick K P, Laroux F S, Fuseler J, Wolf R E, Gray L, Hoffman . et al . Role of reactive metabolites of oxygen and nitrogen in inflammatory bowel disease. Free Radic Biol Med. 2002; 33 311-22
- 3 Ransford R A, Langman M JS. Sulphasalazine and mesalazine: serious adverse reactions re-evaluated on the basis of suspected adverse reaction reports to the Committee on Safety of Medicines. Gut. 2002; 51 36-9
- 4 Galvez J, Sanchez de Medina F, Jimenez J, Zarzuelo A. Studies in natural products chemistry, volume 25. Bioactive natural products (Part F). Effects of flavonoids on gastrointestinal disorders. In: Atta-ur-Rahman, editor Amsterdam; Elsevier 2001: p. 607-49
- 5 Gonzalez R, Sanchez de Medina F, Galvez J, Rodriguez-Cabezas M E, Duarte J, Zarzuelo A. Dietary vitamin E supplementation protects the rat large intestine from experimental inflammation. Int J Vitam Nutr Res. 2001; 71 243-50
- 6 Cuzzocrea S, McDonald M C, Mazzon E, Dugo L, Lepore V, Fonti M T. et al . Tempol, a membrane-permeable radical scavenger, reduces dinitrobenzene sulfonic acid-induced colitis. Eur J Pharmacol. 2000; 406 27-37
- 7 Vilegas W, Roque N F, Salatino A, Giesbrecht A M, Davino S. Isocoumarin from Paepalanthus bromelioides . Phytochemistry. 1990; 29 2299-2301
- 8 Varanda E A, Raddi M S, Dias Fde L, Araujo M C, Gibran S C, Takahashi C S. et al . Mutagenic and cytotoxic activity of an isocoumarin (Paepalantine) isolated from Paepalanthus vellozioides . Teratog Carcinog Mutagen. 1997; 17 85-95
- 9 Leitao G G, Leitao S G, Vilegas W. Quick preparative separation of natural naphthopyranones with antioxidant activity by high-speed counter-current chromatography. Z Naturforsch [C]. 2002; 57 1051-5
- 10 Morris G P, Beck P L, Herridge W, Depew W, Szewczuk M R, Wallace J L. Hapten induced model of chronic inflammation and ulceration in rat colon. Gastroenterology. 1989; 96 795-803
- 11 Bell C J, Gall D G, Wallace J L. Disruption of colonic electrolyte transport in experimental colitis. Am J Physiol. 1995; 268 G622-30
- 12 Sánchez de Medina F, Gálvez J, Romero J A, Zarzuelo A. Effect of quercitrin on acute and chronic experimental colitis in the rat. J Pharm Exp Ther. 1996; 278 771-9
- 13 Rodriguez-Cabezas M E, Galvez J, Lorente M D, Concha A, Camuesco D, Azzouz S. et al . Dietary fiber down-regulates colonic tumor necrosis factor α and nitric oxide production in trinitrobenzenesulfonic acid-induced colitic rats. J Nutr. 2002; 132 3263-71
- 14 Galvez J, de la Cruz J P, Zarzuelo A, Sanchez de la Cuesta F. Flavonoid inhibition of enzymic and nonenzymic lipid peroxidation in rat liver differ from its influence on the glutathione-related enzymes. Pharmacology. 1995; 51 127-33
- 15 Sanchez de Medina F, Perez R, Martinez-Augustin O, Gonzalez R, Lorente M D, Galvez J. et al . Disturbances of colonic ion secretion in inflammation: role of the enteric nervous system and cAMP. Pflugers Arch. 2002; 444 378-88
- 16 Cruz T, Galvez J, Crespo M E, Ocete M A, Zarzuelo A. Effects of silymarin on the acute stage of the trinitrobenzenesulphonic acid model of rat colitis. Planta Med 67. 2001; 67 94-96
- 17 Rachmilewitz D, Karmeli F, Okon E, Bursztyn M. Experimental colitis is ameliorated by inhibition of nitric oxide synthase activity. Gut. 1995; 37 247-55
- 18 Hogaboam C M, Jacobson K, Collins S M, Blennerhassett M G. The selective beneficial effects of nitric oxide inhibition in experimental colitis. Am J Physiol. 1995; 268 G673-84
Julio Galvez, Ph. D.
Department of Pharmacology
School of Pharmacy
University of Granada
18071 Granada
Spain
Phone: +34-958243889
Fax: +34-958248964
Email: jgalvez@ugr.es