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Estudo fitoqu?mico e avalia??o da atividade biol?gica de Tibouchina pereirae Aubl. (Melastomataceae)Dias, ?uder Reis 30 October 2013 (has links)
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?UDER REIS DIAS -DISSERTA??O MESTRADO 2013 -RGV.pdf: 1805178 bytes, checksum: fa9b0a71b8366540b825499da5adb0f8 (MD5) / Made available in DSpace on 2015-07-24T13:45:42Z (GMT). No. of bitstreams: 1
?UDER REIS DIAS -DISSERTA??O MESTRADO 2013 -RGV.pdf: 1805178 bytes, checksum: fa9b0a71b8366540b825499da5adb0f8 (MD5)
Previous issue date: 2013-10-30 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / The Melastomataceae family comprises 4,570 species in approximately 180 genera present in all tropical and subtropical regions of the planet. This family, in Brazil, is the sixth largest family of Angiosperms, with over 1500 species. The genus Tibouchina presents, approximately, 350 species, however, are poorly studied. The Tibouchina pereirae Aubl., a shrub, is popularly used for the treatment of kidney diseases. In this study, we show the antioxidant and antinociceptive effects of T. pereirae. The hexane (EHTP), ethanol (EETP) and aqueous (EATP) extracts were obtained by maceration from the aerial parts of T. pereirae. The flavonoid rich fraction (FFTP) was obtained from fractionation of EHTP. The analysis of FFTP by HPLC-DAD and HPLC-MS/MS led to characterization of these flavonoids. The antioxidant activity of extracts was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay system and the in vivo experiments were conducted on Swiss mice using the acetic acid-induced writhing test and the formalin-induced pain test. Results showed that extracts (EHTP, EETP and EATP) and FFTP present antioxidant activity, when compared to standard butylated hydroxytoluene (BHT) and ascorbic acid (AA). The EHTP and FFTP (i.p., 100mg/Kg) reduced the nociception produced by acetic acid by 90,36% and 94,74%, respectively. The FFTP reduced the formalin effects in both phases by 54, 35% and 92,05%, while the EHTP only protected the second phase by 83,39%. / A fam?lia Melastomataceae apresenta cerca de 4.570 esp?cies, distribu?das em, aproximadamente, 180 g?neros presentes em todas as regi?es tropicais e subtropicais do planeta, sendo que no Brasil ? a sexta maior fam?lia de angiospermas, com mais de 1500 esp?cies. O g?nero Tibouchina possui aproximadamente 350 esp?cies, por?m s?o muito pouco estudadas, sendo que a esp?cie Tibouchina pereirae Aubl. ? popularmente utilizada para o tratamento de problemas renais. Nesse estudo, foram avaliadas as atividades antioxidante e antinociceptiva de T. pereirae. Foram obtidos os extratos hex?nico (EHTP), etan?lico (EETP) e aquoso (EATP) a partir da macera??o das partes a?reas de T. pereirae. A fra??o rica em flavonoides (FFTP) foi obtida a partir do fracionamento do EHTP. A an?lise por CLAE-DAD e CLAE-EM/EM desta fra??o possibilitou caracterizar estes flavonoides. A atividade antioxidante dos extratos foi avaliada utilizando o sistema de ensaio 2,2-difenil-1-picrilhidrazil (DPPH) e os experimentos in vivo foram realizados em camundongos Swiss utilizando os testes de contor??o abdominal induzida por ?cido ac?tico e da formalina. Os resultados obtidos demonstraram que o EHTP, EETP e EATP, assim como a fra??o FFTP apresentaram atividade seq?estradora radicalar, quando comparados aos padr?es butilhidroxitolueno (BHT) e ?cido asc?rbico (AA). O EHTP e a FFTP reduziram a nocicep??o induzida pelo ?cido ac?tico em 90,6% e 94,74%, respectivamente. A FFTP reduziu os efeitos da formalina em ambas fases em 54,35% e 92,05%, respectivamente, enquanto que o EHTP foi ativo somente na segunda fase do teste, com uma redu??o no tempo de lambida de 83,39%.
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Caracteriza??o do efeito antinociceptivo e anti-inflamat?rio do polissacar?deo extra?do da levedura Kluyveromyces marxianusOliveira, Renata Freitas de Araujo 26 May 2015 (has links)
Submitted by Luis Ricardo Andrade da Silva (lrasilva@uefs.br) on 2017-01-11T20:36:16Z
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Renata Freitas disserta??o.pdf: 2389915 bytes, checksum: a5eb147a088e89c9ec715df2a0eb6c3f (MD5)
Previous issue date: 2015-05-26 / The yeasts produce different types of metabolites and macromolecules with huge biotechnological potential. Among them, the Kluyveromyces marxianus, species attracts industrial and economic interests for presenting certain qualities, such as thermal tolerance, high growth rates, broad substrate spectrum and modulation of immune response. This work investigated the effects of treatment with the polysaccharide extracted from the Kluyveromyces marxianus yeast (poly322) in pain and inflammation experimental models. The poly322 pharmacological properties were evaluated with writhing, formalin, nociception (manifested by CFA), tail flick, hot-plate and paw edema tests. The cytokine levels were determined by ELISA and the effects on motor performance were evaluated by rotarod and open field tests. The pretreatment with poly322 resulted in reduced nociception induced by acetic acid, CFA and formalin (late phase). Furthermore, animals treated with poly322 exhibited a significant reduction in mechanical hypernociception, paw edema, and local IL-6 levels increase induced by carrageenan. In contrast, treatment with poly322 did not alter the thermal stimulus response threshold in the tail flick and hot plate tests, indicating no central action. Confirming the specificity of the action suggested by nociceptive tests, the treatment with poly322 did not induce motor impairment. These results demonstrate that the poly322 has a potent antinociceptive and anti-inflammatory effects, possibly mediated by the inhibition of the production and/or release of the IL-6 cytokine. / As leveduras produzem diferentes tipos de metab?litos e macromol?culas com enorme potencial biotecnol?gico. Dentre essas, destaca-se a Kluyveromyces marxianus, esp?cie que desperta interesse industrial e econ?mico por apresentar qualidades, como a toler?ncia t?rmica, altas taxas de crescimento, amplo espectro de substrato e modula??o da resposta imune. O presente estudo investigou os efeitos do tratamento com o polissacar?deo extra?do da levedura Kluyveromyces marxianus (poly322) em modelos experimentais de dor e inflama??o. As propriedades farmacol?gicas do poly322 foram avaliadas nos testes de contor??es abdominais, formalina, nocicep??o manifesta por CFA, retirada da cauda, placa quente e edema de pata. Os n?veis de citocinas foram determinados por ELISA e os efeitos sobre o desempenho motor foram avaliados pelos testes do cil?ndro girat?rio e campo aberto. O pr?-tratamento com o poly322 resultou na redu??o da hipernocicep??o induzida pelo ?cido ac?tico, CFA e formalina (segunda fase). Al?m disso, os animais tratados com o poly322 exibiram uma redu??o significativa no edema de pata e no aumento local dos n?veis de IL-6 induzidos pela carregenina. Em contraste, o tratamento com o poly322 n?o alterou o limiar de resposta a est?mulo t?rmico nos testes de retirada da cauda e placa quente, indicando aus?ncia de a??o central. Confirmando a especificidade da a??o sugerida pelos testes nociceptivos, o tratamento com o poly322 n?o induziu comprometimento motor. Os resultados demonstram que o poly322 possui um potente efeito antinociceptivo e anti-inflamat?rio, possivelmente mediado pela inibi??o da produ??o e/ou libera??o da citocina IL-6.
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Avalia??o do potencial analg?sico e anti-inflamat?rio do composto piraz?lico 1,5-difenil-3-hidrazinopirazol(a) - DHPCastro, Raphael Andrade de 18 February 2011 (has links)
Submitted by Sandra Pereira (srpereira@ufrrj.br) on 2016-08-24T15:39:27Z
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Previous issue date: 2011-02-18 / causing pain as a constant feature. The pyrazole compounds are the drugs of synthetic origin in their chemical structure consisting of a ring pirazol?nico, with which several studies show the effectiveness in controlling of pain, fever and inflammation. The need to develop new drugs with analgesic and anti-inflammatory, low cost and which have few adverse reactions, has stimulated the synthesis and study of pharmacological activities of pyrazole compounds. With this objective, we studied the antinociceptive and anti-inflammatory potential of compound 1.5-diphenyl-pyrazole-3-hidrazinopirazol(a) (DHP), administered orally in pharmacological models of the acetic acid writhing, tail-flick, formalin, ear edema induced by croton oil and carrageenan-induced peritonitis in mice, and mechanical allodynia (von Frey) and thermal hyperalgesia (Hargreaves) in rats. The administration of DHP (1, 3 and 10mg/kg) decreased in a dose-dependent (41.3, 62.7 and 76%) number of writhing (ID50 = 1.3mg/kg). In the tail-flick test, DHP (10mg/kg) was ineffective and the application of positive control fentanyl (200?g/kg, sc) increased the latency to thermal stimulation in up to 138%. Without changing the first phase of nociception (neurogenic pain) of the formalin test, DHP (10mg/kg) and the positive control indomethacin (10mg/kg, p.o.) inhibited the reactivity in the 2 phase (ndinflammatory pain) in 40.9 and 48.7% respectively. This same dose of DHP reduced by 54% the ear edema induced by croton oil, as well as the positive control, dexamethasone (2mg/kg, sc) at 55.3%. Also in a dose-dependent DHP (3, 10 and 30 mg / kg) inhibited by 11.8, 39 and 53.7%, respectively, leukocyte migration in peritonitis induced by carrageenan test (ID50 = 22.9mg/kg). In the assessment of mechanical allodynia incision group treated with DHP (GIDHP - 10mg/kg) showed a significant reversal of allodynia (RA) after one hour of administration, with maximum reading RA for 12 hours (28.2%) in the second stage of the experiment, remaining in the third stage with RA of 26.9, 43.4 and 60.4% in the 7th, 10th and 14th days of evaluations, when compared with the vehicle group incised (GIV). In thermal hyperalgesia GIDHP (10mg/kg) also significantly reversed the hyperalgesia (RH) after one hour of treatment, with RH maximum of three hours in reading (68.9%) in the second stage, obtaining in the third stage RA of 43.4, 32,1 and 64% in 7th, 10th and 14th days of evaluations, when compared to the GIV and obtaining similar values of the group not incised vehicle (GNIV) on 14 dayth. In the von Frey and Hargreaves GNIV showed similar readings in the three stages of the experiment. The DHP (10mg/kg) did not alter the motor activity of mice in rota-rod test. Whereas the compound DHP showed antinociceptive activity in writhing test, antiedematogenic in ear edema, inhibited the 2nd phase of nociception (inflammatory pain) in formalin test and leukocyte migration, promoting reversal of hypernociception in models of thermal hyperalgesia and allodynia mechanics, these results indicate that the effectiveness of DHP involves the participation of anti-inflammatory mechanisms and create favorable outlook for its future use with this therapeutic goal. / A inflama??o ? um processo fisiol?gico de resposta org?nica diante de les?o tissular ou infec??o, gerando a dor como caracter?stica constante. Os compostos piraz?licos s?o drogas de origem sint?tica com um anel pirazol?nico na sua estrutura qu?mica, com os quais diversos estudos demonstram a efic?cia no controle da dor, da febre e da inflama??o. A necessidade do desenvolvimento de novos f?rmacos com propriedades analg?sicas e anti-inflamat?rias, de baixo custo e que apresentem poucas rea??es adversas, tem estimulado a s?ntese e o estudo das atividades farmacol?gicas dos compostos piraz?licos. Com esse objetivo, foi estudado o potencial antinociceptivo e anti-inflamat?rio do composto piraz?lico 1,5-difenil-3-hidrazinopirazol(a) (DHP), administrado pela via oral, nos modelos farmacol?gicos das contor??es abdominais pelo ?cido ac?tico, tail-flick, formalina, edema de orelha induzido pelo ?leo de cr?ton e peritonite induzida pela carragenina em camundongos; e na alodinia mec?nica (von Frey) e hiperalgesia t?rmica (Hargreaves) em ratos. A administra??o do DHP (1, 3 e 10mg/kg) diminuiu de maneira dose-dependente (41,3, 62,7 e 76%) o numero de contor??es abdominais (ID50=1,3mg/kg). No teste de tail-flick, DHP (10mg/kg) n?o foi efetivo e a aplica??o do controle positivo fentanil (200?g/kg, s.c.) ampliou a lat?ncia ao est?mulo t?rmico em at? 138%. Sem alterarem a 1? fase de nocicep??o (dor neurog?nica) do teste da formalina, o DHP (10mg/kg) e o controle positivo indometacina (10mg/kg, p.o.) inibiram a reatividade na 2? fase (dor inflamat?ria) em 40,9 e 48,7% respectivamente. Essa mesma dose do DHP reduziu em 54% o edema de orelha induzido pelo ?leo de cr?ton, assim como o controle positivo dexametasona (2mg/kg, s.c.) em 55.3%. Tamb?m de forma dose-dependente o DHP (3, 10 e 30 mg/kg) inibiu em 11,8, 39 e 53,7% respectivamente, a migra??o de leuc?citos no teste da peritonite induzida pela carragenina (ID50=22,9mg/kg). Na avalia??o da alodinia mec?nica o grupo incisado tratado com o DHP (GIDHP - 10mg/kg) apresentou significativas revers?es da alodinia (RA) ap?s uma hora da administra??o, com RA m?xima na leitura de 12 horas (28,2%) na segunda etapa, mantendo-se na terceira etapa com RA de 26,9, 43,4 e 60,4% nos 7?, 10? e 14? dias de experimenta??o, comparados com o grupo incisado ve?culo (GIV). Na hiperalgesia t?rmica o GIDHP tamb?m produziu revers?o da hiperalgesia (RH) uma hora ap?s o tratamento, com RH m?ximo na leitura de 3 horas (68,9%) na segunda etapa, mantendo-se na terceira etapa com RH de 43,4, 32,1 e 64% nos 7?, 10? e 14? dias de experimenta??o, quando comparados ao GIV e obtendo valores semelhantes ao grupo n?o incisado ve?culo (GNIV) no 14? dia. No von Frey e no Hargreaves o GNIV apresentou leituras semelhantes nas tr?s etapas do experimento. O DHP (10mg/kg) n?o alterou a atividade motora de camundongos no teste do rota-rod. Considerando que o composto DHP apresentou atividade antinociceptiva no teste das contor??es, antiedematog?nica no edema de orelha, inibiu a 2? fase de nocicep??o (dor inflamat?ria) do teste da formalina e a migra??o leucocit?ria, promovendo ainda revers?o da hipernocicep??o nos modelos de hiperalgesia t?rmica e alodinia mec?nica; esses resultados indicam que a efetividade do DHP envolve a participa??o de mecanismos anti-inflamat?rios e criam perspectivas favor?veis para sua futura utiliza??o com esse objetivo terap?utico.
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