Atividade antiulcerogenica de extratos e frações obtidas dos escapos das especies Syngonanthus bisulcatus Rul. e Syngonanthus arthrotrichus Silveira em modelos animais

Orientador: Alba Regina Monteiro Souza BritoTese (doutorado) - Universidade Estadual de Campinas, Instituto de BiologiaResumo: Syngonanthus bisulcatus e Syngonanthus arthrotrichus, espécies pertencentes à família Eriocaulaceae, são encontradas em regiões tropicais na América do Sul e no Brasil, principalmente nos estados da Bahia e Minas Gerais. Este gênero é conhecido popularmente como ¿sempre vivas¿. S. bisulcatus e S. arthrotrichus foram investigadas porque os dados quimiotaxonômicos e filogenéticos da família apontavam a presença de flavonóides, que possuem atividades biológicas relevantes. Os extratos etanólicos dessas espécies, nas doses de 50, 100 e 250 mg/kg, e as frações ricas (FRF) e deficientes (FDF) em flavonóides, na dose de 100 mg/kg via oral, foram estudadas em modelos de úlceras induzidas agudamente (HCl/etanol, etanol, estresse, indometacina/betanecol e isquemia e reperfusão) e subcronicamente (ácido acético 30%), em camundongos e ratos. A via intraduodenal foi empregada somente para frações no modelo de ligadura do piloro. Tanto extratos, quanto frações, inibiram significativamente as lesões ulcerativas induzidas pelos diferentes agentes. Também foram observadas alterações significantes nos parâmetros bioquímicos da secreção ácida gástrica com redução na concentração total de H+ no suco gástrico com conseqüente elevação do pH. Estes resultados sugeriram atividades anti-secretória e citoprotetora para extratos e frações. O pré-tratamento com as frações FRF de ambas as espécies produziu, no modelo de úlcera por ácido acético, redução na área da lesão por estimulação do processo de cicatrização. Adicionalmente, verificou-se que a atividade antiulcerogênica das frações não está relacionada ao aumento da PGE2; porém, o muco aderido, provavelmente estimulado pelo óxido nítrico, bem como os grupos sulfidrilas protéicos parecem estar envolvidos com a atividade citoprotetora de FRF, de FDF ou de ambas, dependendo do mecanismo de ação investigado. Animais tratados com as FRF das espécies em estudo e submetidos à indução de úlcera por etanol tiveram aumento significativo dos níveis séricos do hormônio somatostatina e redução no de gastrina. As FRF, estudadas em ratos submetidos à isquemia e reperfusão, produziram diminuição do número de lesões, indicando atividade antioxidante verificada através da redução da peroxidação lipídica e aumento dos níveis de grupamentos tióis totais. Por último, experimentos de citotoxicidade demonstraram que as frações da S. bisulcatus foram mais citotóxicas do que as frações da S. arthrotrichus em cultura de células V79. Análises cromatográficas e RMN demonstraram que as FRF contém luteolina e luteolina glicosilada para ambas as espécies, além de lutonarina (5,3¿,4¿-triidroxi-6-C,7-O-di-B-D-glucopiranosilflavona) e 6-hidroxi-7-O-B-D-glucopiranosilluteolina (5,6,3¿,4¿-tetrahidroxi-7-O-B-D-gluco-piranosil) para S. bisulcatus. Para a S. arthrotrichus, foram isoladas ainda apigenina e uteolina-6-C-?-D-glucopiranosideo. O conjunto de dados permite concluir que a atividade antiulcerogênica dos extratos e frações da S. bisulcatus e S. arthrotrichus está relacionada à atividade anti-secretória, citoprotetora e antioxidante dos flavonóides existentes nessas espéciesAbstract: The genus Syngonanthus (family Eriocaulaceae) is found in tropical regions of South America. In Brazil, the species Syngonanthus bisulcatus and Syngonanthus arthrotrichus, popularly known as ¿sempre vivas¿, occur mainly in the states of Bahia and Minas Gerais. Chemiotaxonomic and phylogenetic data have indicated the presence of flavonoids in both of these species. In this work, we investigated the effects of ethanolic extracts (50, 100 and 250 mg/kg, orally) and of flavonoid-rich (FRF) and -deficient (FDF) fractions (100 mg/kg, orally) of these species in models of acute (HCl/ethanol, ethanol, stress, indomethacin/bethanecol) and subchronic (30% acid acetic) ulcers in mice and rats, as well as in a model of pylorus ligature in which the fractions were administered intraduodenally. The extract and fractions significantly prevented ulceration caused by various agents, and also significantly reduced the total H+ concentration in gastric juice, which led to a rise in pH. These results indicated that the extract and fractions had antisecretory and cytoprotective actions. In acetic acid-induced ulcers, treatment with the fractions (FRF) from both species reduced the area of damage by enhancing the healing process. The antiulcerogenic activity of the fractions was not associated with an increase in PGE2 formation. In contrast, the amount of adhered mucus (probably stimulated by nitric oxide), together with the sulphydryl groups of proteins, appeared to be involved in the cytoprotection by FRF and FDF, depending on the mechanism of action. In animals pre-treated with the FRF of either species and then subjected to ulcer induction with ethanol, there was a significant increase in the serum levels of somatostatin and a reduction in those of gastrin. In rats with ischemia and reperfusion, FRF of both species increased the extent of injury, thus indicating an antioxidant activity that was reflected in a reduction in lipid peroxidation and an increase in the levels of total thiols. In cultured Chinese hamster V79 fibroblasts, the fractions of S. bisulcatus were more cytotoxic than those of S. arthrotrichus. Chromatographic analysis and NMR of the fractions of both species showed that the FRF contained luteolin and glycosylated luteolin, as well as previously detected flavonoids such as lutonarin 5'3¿,4¿-trihydroxy-6-C,7-O-di-B-D-glucopyranosylflavone) and 6-hydroxy-7-O-B-D-glucopyranosylluteolin (5,6,3¿,4¿-tetrahydroxy-7-O-B-D-glucopyranosyl), in the case of S. bisulcatus. In addition to luteolin, apigenin and luteolin-6-C-?-D-glucopyranoside were also detected in S. arthrotrichus. These results indicated that the antiulcerogenic activity of extracts and fractions of S. bisulcatus and S. arthrotrichus was related to the antisecretory, cytoprotective and antioxidant actions of flavonoids present in these plantsDoutoradoFisiologiaDoutor em Biologia Funcional e Molecula

Liderança, competências empreendedoras e inovação social: um estudo com gestores públicos Leadership, entrepreneurial skills and social innovation: a study with public managers

A globalização tem provocado complexidade econômica, política e social na gestão das organizações, sejam com fins lucrativos ou não, e para se adaptarem elas têm se preocupado cada vez mais em procurar novos mecanismos de gestão. A administração pública, diante deste cenário, também foi desafiada a promover mudanças, sendo válido frisar que dentre tais modificações, há a exigência de novas práticas de liderança e competências empreendedoras que possam mobilizar políticas voltadas à melhoria nas relações do Estado com a sociedade, evidenciando o necessário envolvimento entre todos os atores desta dinâmica social.  O presente trabalho objetivou estudar o processo de inovação social na área da cultura, analisando as relações entre liderança e competências empreendedoras dos administradores públicos. Para tanto se escolheu como objeto para pesquisar um dos eventos desenvolvido pela Secretaria de Estado e Cultura do Estado do Amazonas: o Concerto de Natal. Os procedimentos metodológicos incluíram a abordagem qualitativa e quantitativa e a população investigada foram os gestores da secretaria até o nível de gerência. Também foram feitas observações de campo e entrevistas com empresas prestadoras de serviços. Os resultados permitiram identificar as práticas de lideranças exercidas pelos gestores; mapear suas competências empreendedoras; mensurar as relações entre esses constructos; e, aferir suas influências na promoção da inovação social analisando os eixos condições de vida e geração de trabalho e emprego. Com base nos achados pode-se concluir que existe associação entre os constructos considerados e que eles influenciam positivamente à inovação social

Ulcer Healing And Mechanism(s) Of Action Involved In The Gastroprotective Activity Of Fractions Obtained From Syngonanthus Arthrotrichus And Syngonanthus Bisulcatus

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Background: Syngonanthus arthrotrichus and Syngonanthus bisulcatus, currently known for Comanthera aciphylla (Bong.) L.R.Parra & Giul. and Comanthera bisulcata (Koern.) L.R. Parra & Giul, popularly known in Brazil as "sempre-vivas," are plants from the family Eriocaulaceae. They are found in the states of Minas Gerais and Bahia. The species are known to be rich in flavonoids to which their gastroprotective activity has been attributed. In this research, experimental protocols were performed to elucidate the associated mechanisms of action. Methods: The activity was evaluated using induced gastric ulcer models (acetic acid and ethanol-induced gastric lesions in NEM or L-NAME pre-treated mice, and by ischemia/reperfusion). Antioxidant enzymes, serum somatostatin, and gastrin were also evaluated. Results: In chronic gastric ulcers, a single daily oral dose of Sa-FRF or Sb-FRF (100 mg/kg body wt.) for 14 consecutive days accelerated ulcer healing to an extent similar to that seen with an equal dose of cimetidine. The pre-treatment of mice with NEM (N-ethylmaleimide) or L-NAME (N-nitro-L-arginine) abolished the protective activity of Sa-FRF, Sa-FDF, Sb-FDF and Sb-FRF or Sa-FRF and Sb-FRF, respectively, which indicates that antioxidant compounds and nitric oxide synthase activity are involved in the gastroprotective. Sa-FRF and Sb-FRF (100 mg/kg p.o) protected the gastric mucosa against ulceration that was induced by ischemia/reperfusion (72 and 76 %, respectively). It also decreased lipid peroxidation and restored total thiols in the gastric wall of mice that had been treated with ethanol. When administered to rats submitted to ethanol-induced gastric lesions, Sa-FRF and Sb-FRF (100 mg/kg, p.o.) increased the somatostatin serum levels, while the gastrin serum levels were proportionally decreased. Conclusions: The results indicate significant healing effects and gastroprotective activity for the Sa-FRF and Sb-FRF, which probably involves the participation of SH groups, nitric oxide (NO), the antioxidant system, somatostatin, and gastrin. All are integral parts of the gastrointestinal mucosa's cytoprotective mechanisms against aggressive factors.15Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Tannins, Peptic Ulcers and Related Mechanisms

This review of the current literature aims to study correlations between the chemical structure and gastric anti-ulcer activity of tannins. Tannins are used in medicine primarily because of their astringent properties. These properties are due to the fact that tannins react with the tissue proteins with which they come into contact. In gastric ulcers, this tannin-protein complex layer protects the stomach by promoting greater resistance to chemical and mechanical injury or irritation. Moreover, in several experimental models of gastric ulcer, tannins have been shown to present antioxidant activity, promote tissue repair, exhibit anti Helicobacter pylori effects, and they are involved in gastrointestinal tract anti-inflammatory processes. The presence of tannins explains the anti-ulcer effects of many natural products

Antiulcerogenic action of ethanolic extract of the resin from Virola surinamensis Warb. (Myristicaceae)

Ethnopharmacological relevance: Virola surinamensis (Myristicaceae), popularly known as mucuiba, ucuuba or ucuuba do igapo is a large tree that grows abundantly in Varzea forest and on river banks in the Brazilian states of Amazonas and Tocantins. The resin obtained by cuts on the stem bark is a reputed folk remedy in its natural form for the treatment of ulcer, gastritis inflammation and cancer.Aim of the study: The present work evaluated the pharmacological activity of the resin obtained from bark of V surinamensis as antiulcerogenic in experimental in vivo model in order to observe whether its traditional use is justified.Materials and methods: The preventive action of ethanolic extract of V surinamensis was evaluated in experimental in vivo models in rodents that simulated this disease in human gastric mucosa.Results: Oral administration of acidified ethanol solution produced severe hemorrhagic lesions in glandular mucosa with ulcerative lesion of 50 +/- 11.5 mm. In animals pretreated with V surinamensis (500 mg/kg, p.o.) a significant inhibition of mucosal injury of 2.40 +/- 0.56 mm (95% inhibition) was detected. The V. surinamensis, at the same dose, also reduced significantly (p < 0.05) the formation of gastric lesions induced by indomethacin (39%), stress (45%) and by pylorus ligature in mice (31%) when compared to animals treated with vehicle. The extract from V surinamensis exerts gastroprotective action only when this extract contacts gastric mucosa (oral route) with. increased pH values and reduced H(+) concentration of gastric contents. The ethanolic extract of V surinamensis resin was analyzed by TLC and spectrometric methods (NMR and ES-MS) and the main constituent of this extract was epicatechin.Conclusions: We suggest that the epicatechin present in V surinamensis resin may be among active principles responsible for the antiulcer activity shown by the tested resin but their used suggest carefulness because toxicological symptoms mentioned by population. (C) Published by Elsevier B.V

Anti-inflammatory intestinal activity of Combretum duarteanum Cambess. in trinitrobenzene sulfonic acid colitis model

AIM To evaluate the anti-inflammatory intestinal effect of the ethanolic extract (EtOHE) and hexane phase (HexP) obtained from the leaves of Combretum duarteanum (Cd). METHODS Inflammatory bowel disease was induced using trinitrobenzenesulfonic acid in acute and relapsed ulcerative colitis in rat models. Damage scores, and biochemical, histological and immunohistochemical parameters were evaluated. RESULTS Both Cd-EtOHE and Cd-HexP caused significant reductions in macroscopic lesion scores and ulcerative lesion areas. The vegetable samples inhibited myeloperoxidase increase, as well as pro-inflammatory cytokines TNF-alpha and IL-1 beta. Anti-inflammatory cytokine IL-10 also increased in animals treated with the tested plant samples. The anti-inflammatory intestinal effect is related to decreased expression of cyclooxygenase-2, proliferating cell nuclear antigen, and an increase in superoxide dismutase. CONCLUSION The data indicate anti-inflammatory intestinal activity. The effects may also involve participation of the antioxidant system and principal cytokines relating to inflammatory bowel disease23813531366sem informaçã

Chemical composition of Rosmarinus officinalis essential oil and antioxidant action against gastric damage induced by absolute ethanol in the rat

Objective: To evaluate the antioxidant activity of the essential oil obtained from Rosmarinus officinalis (R. officinalis) in ethanol-induced gastric ulcer model in vivo. Methods: The antioxidant properties of the essential oil obtained from R. officinalis were evaluated against gastric injury induced by absolute ethanol. Gastric tissues were prepared to enzymatic assays. The levels of glutathione, lipid peroxides, and the activities of glutathione peroxidase, superoxide dismutase and myeloperoxidase were measured. Results: Ethanol produced severe hemorrhagic lesions in the stomach with ulcerative lesion of (140.2 ± 37.2) mm2. In animals pretreated with essential oil of R. officinalis (50 mg/kg, p.o.), a significant inhibition of mucosal injury of (21.2 ± 7.1) mm2 (84% inhibition) was observed. The essential oil of R. officinalis protected the gastric mucosa probably by modulating the activities of the enzymes (superoxide dismutase and glutathione peroxidase) and increasing or maintaining the levels of glutathione. In addition, lipid peroxides levels were reduced. The essential oil of R. officinalis was analyzed by gas chromatography–mass spectrometer and the main constituents were cineole (28.5%), camphor (27.7%) and alpha-pinene (21.3%). Conclusions: We suggest that the monoterpenes present in the essential oil obtained from R. officinalis may be among the active principles responsible for the antioxidant activity shown by essential oil of R. officinalis

Gastroprotective effects (in rodents) of a flavonoid rich fraction obtained from Syngonanthus macrolepsis

Objectives: Syngonanthus macrolepis, popularly known in Brazil as sempre-vivas', is a plant from the family Eriocaulaceae, it is found in the states of Minas Gerais and Bahia. The species contains a variety of constituents, including flavonoids with gastroprotective effect. In this work, a flavonoid-rich fraction (Sm-FRF) obtained from scapes of S.macrolepis was investigated for preventing gastric ulceration in mice and rats.MethodsThe activity was evaluated in models of induced gastric ulcer (absolute ethanol, stress, non-steroidal anti-inflammatory drugs and pylorus ligation). The cytoprotective mechanisms of the Sm-FRF in relation to sulfhydryl (SH) groups, nitric oxide (NO) and antioxidant enzymes were also evaluated.Key findingsThe Sm-FRF (100mg/kg, p.o.) significantly reduced gastric injury in all models, and did not alter gastric juice parameters after pylorus ligation.ConclusionsThe results indicate significant gastroprotective activity for the Sm-FRF, which probably involves the participation of both SH groups and the antioxidant system. Both are integral parts of the gastrointestinal mucosa's cytoprotective mechanisms against aggressive factors

Mechanisms of the Gastric Antiulcerogenic Activity of Anacardium humile St. Hil on Ethanol-Induced Acute Gastric Mucosal Injury in Rats

Leaves and bark infusions Anacardium humile St. Hil. (Anacardiaceae), known as in Brazil as cajuzinho do cerrado, have been used in folk medicine as an alternative treatment for ulcers and gastritis. This study evaluated the gastroprotective activity of an ethyl acetate extract of the leaves of A. humile (AcF) and the mechanism involved in this gastroprotection. Pretreatment concentrations (50, 100, 200 mg.kg(-1)) were administered by gavage. Following a 60 min. period, all the rats were orally administered 1 mL of absolute ethanol. One hour after the administration of ethanol, all groups were sacrificed, and the gastric ulcer index was calculated. Prostaglandin PGE(2) concentration, gastric adherent mucous, and the participation of nitric oxide (NO) and sulfhydryl compounds in the gastroprotection process were also analyzed using the most effective tested dose (50 mg.kg(-1)). A histological study of the glandular stomach for the evaluation of the epithelial damage and mucus content was also performed. AcF significantly reduced the gastric damage produced by ethanol. This effect was statistically significant for the 50 mg.kg(-1) group compared to control. Also, it significantly increased the PGE(2) (by 10-fold) and mucous production, while pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) or N-ethylmaleimide (NEM) completely abolished the gastroprotection. AcF has a protective effect against ethanol, and this effect, might be due to the augmentation of the protective mechanisms of mucosa.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq