Orientador: João Ernesto de Carvalho, Mary Ann Foglio / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T08:48:34Z (GMT). No. of bitstreams: 1
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Previous issue date: 2004 / Resumo: Os extratos brutos e fiações semipurificadas obtidos de Artemisia annua L apresentaram atividade antiulcerogênica em diferentes modelos experimentais, possivelmente relacionada aos mecanismos citoprotetores, especialmente a síntese de prostaglandinas na mucosa gástrica. Portanto, os objetivos deste trabalho corresponderam ao isolamento, à identificação e à determinação do mecanismo de ação antiulcerogênica do(s) princípio(s) ativo(s) obtidos da referida espécie vegetal. Uma fiação enriquecida em lactonas sesquiterpênicas (FLAc), obtida do extrato bruto hidroetanólico, foi purificada em coluna cromatográfica, fornecendo quatro fiações denominadas FIAu.c, FIBLAc, FICu.c e FIDLAc, que reduziram o índice de lesões ulcerativas no modelo de úlcera induzida por etanol em ratos. As fiações FICLAc e FIDL / Abstract: Artemisia annula L. crude hydroethanolic extract reduced the ulcerative lesion index on ethanol induced ulcer mode!. This extract was purified with the intention of having an enriched fraction of sesquiterpene lactones, since previous work had indicate the presence of this chemical group. The resulting fraction was more efficient Ín decreasing the ulcerative lesion index when evaluated under the same experimental conditions. With these informations in mind, this study was undertaken to isolate and identify the active(s) substance(s) and to determine the probable pharmacological mechanism. The enriched sesquiterpene lactone fraction was purified through column chromatography, using silicagel, and supplied four different polarity fractions as follows, FIALAc, FIBLAc, FICu.c e FIDa.c. All these fractions, when submitted to the ethanol induced ulcer in rats, resulted in different inhibition levels ofthe ulcerative lesion index. FIClac and FIDLAc were purified through column chromatograpy using silicagel and increasing gradientes of hexane / ethyl acethate. The obtained fractions were monitorated by thin layer chromatography. The physical and spectral data (mass, lH-RMN and 13C-RMN) of compounds obtained from FICLAC and FIDLAc were consistent with those of dhydro-epideoxyarteannuin b and deoxyartemisinin, respectively. Dhydro-epideoxyarteannuin b and deoxyartemisinin were administrated orally on ethanol induced ulcer model in different dose levels. These two compounds presented dose-dependent inhibition of ulcerative lesion index, with ED50 values of 55,6 and 87,5 mg/Kg, respectively. The previous treatment with indomethacin, a cyclooxygenase inhibitor, blocked the antiulcerogenic activity of dihydro-epideoxyarteannuin b and deoxyartemisinin on ethanol induced ulcer model. These results suggest that the antiulcerogenic activity of these compounds have a straight relationship with an increase of prostaglandin synthesis.
This hypothesis was reinforced by the increase of adherent mucus on the gastric mucosa produced when dihydro-epideoxyarteannuin b and deoxyartemisinin were administrated orally, on ethanol induced ulcer model. Since the mucus synthesis is mediated by prostaglandins, the active substances could be acting by stimulating synthesis of these autacoids. Intraduodenal administration of dhydro-epideoxyarteannuin b and deoxyartemisinin on pylorus ligation model in rats, was adopted to evaluate gastric acid and pepsin secretion. These substances did not modify the secretion volume. Only deoxyartemisinin reduced the hydrogenionic concentration of gastric content. The peptic activity was increased in both groups of animals, treated with dhydro-epideoxyarteannuin b and deoxyartemisinin. Dhydro-epideoxyarteannuin b and deoxyartemisinin were evaluated in platelet agregation and increased the ADP induced agregation. This activity was reverted with the indomethacin presence.
The prostaglandin E2 was quantified from gastric mucosa, in animals treated orally wth dihydro-epideoxyarteannuin b and deoxyartemisinin, with and without previous indomethacin treatment. In these experimetal conditions, only dhydro-epideoxyarteannuin b produced an increase on production of prostaglandins / Doutorado / Ciencias Basicas / Doutor em Clínica Médica
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.unicamp.br:REPOSIP/309828 |
| Date | 30 April 2004 |
| Creators | Dias, Patricia Correa |
| Contributors | UNIVERSIDADE ESTADUAL DE CAMPINAS, Foglio, Mary Ann, 1960-, Carvalho, João Ernesto, 1954-, Oliveira, Ricardo Ferraz de, Emim, Jose Artur da Silva, Rehder, Vera Lúcia Garcia, Mattos Filho, Thales Rocha de |
| Publisher | [s.n.], Universidade Estadual de Campinas. Faculdade de Ciências Médicas, Programa de Pós-Graduação em Clínica Médica |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | 85f. : il., application/pdf |
| Source | reponame:Repositório Institucional da Unicamp, instname:Universidade Estadual de Campinas, instacron:UNICAMP |
| Rights | info:eu-repo/semantics/openAccess |
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