Extrato seco padronizado de Amburana cearensis cultivada e constituintes químicos modulam a inflamação em um novo modelo de asma exacerbada em camundongos BALB/C e a resposta neutrofílica in vitro

Detalhes bibliográficos
Autor(a) principal: Amaral, Hilmara Helia de Sousa
Data de Publicação: 2017
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
Texto Completo: http://www.repositorio.ufc.br/handle/riufc/28570
Resumo: Asthma is a chronic inflammatory disease that affects more than 300 million people around the world. The main cause of hospitalization and mortality related to the disease are the exacerbations characterized mainly by an inflammatory response profile where Th2, Th17 and neutrophil lymphocytes play an important role in addition to resistance to corticosteroid therapy. This justifies the importance of research on new drugs for the treatment of allergic asthma, especially exacerbation. In this context, medicinal plants such as Amburana cearensis appear as a potential source of new drugs for the treatment of exacerbated allergic asthma. Faced with the risk of extinction of this wild species, in the last years several chemical and pharmacological studies have been carried out generating promising results with cultivated species, which has as active principles coumarin (CM) and vanillic acid (AV). The aim of this study was to investigate the effects of the standardized extract of cultured A. cearensis (ESPACC, markers: CM and AV), CM and AV on exacerbated allergic asthma in BALB / c mice, including the evaluation of these in the neutrophilic response. The pattern of allergic asthma induced by OVA and exacerbated by LPS in BALB / c mice was investigated, investigating different experimental conditions that were evaluated mainly by the analysis of the accumulation of inflammatory cells in the bronchoalveolar lavage (BAL) of the animals. The effects of ESPACC and CM (vo or ip) on the accumulation of inflammatory cells, tissue morphology and levels of IL-4 and TNF-α cytokines in BAL of animals sensitized and challenged with LPS + OVA , in addition to the evaluation of the effects of ESPACC, CM and AV on the degranulation and production of reactive oxygen species (EROS) in PMA-activated neutrophils. In the standardization of the exacerbated asthma model, it was seen that the dose of OVA and LPS, as well as the increase in the duration of exposure to the antigens, were determinant for obtaining the model of exacerbated allergic asthma. Treatment of CM animals (10 or 20 mg / kg, ip or v0, respectively) did not significantly reduce leukocyte accumulation in BAL compared to the control group, but selectively modulated neutrophil migration. ESPACC (100 mg / kg, ip) was able to significantly inhibit leukocyte accumulation in BAL, mucus production and cytokine secretion. In neutrophil culture, ESPACC, CM and AV significantly reduced the neutrophil degranulation induced by PMA measured by the release of MPO, as well as EROS production. The results indicate that cultured A. cearensis, CM and AV have an anti-inflammatory effect in an exacerbated allergic asthma model, modulating inflammatory cell accumulation and neutrophil response, as well as the production of mucus, cytokines and EROS. The results showed that cumaru and its chemical constituents are a potential source for the development of anti-inflammatory drugs to be used in the treatment of exacerbated allergic asthma.
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spelling Extrato seco padronizado de Amburana cearensis cultivada e constituintes químicos modulam a inflamação em um novo modelo de asma exacerbada em camundongos BALB/C e a resposta neutrofílica in vitroAmburana cearensis cultivated standard dried extract and chemical constituents modulate inflammation in a new exacerbated asthma model in mice BALB/C and in vitro neutrophilic responseAsmaÁcido VanílicoFarmacologiaAsthma is a chronic inflammatory disease that affects more than 300 million people around the world. The main cause of hospitalization and mortality related to the disease are the exacerbations characterized mainly by an inflammatory response profile where Th2, Th17 and neutrophil lymphocytes play an important role in addition to resistance to corticosteroid therapy. This justifies the importance of research on new drugs for the treatment of allergic asthma, especially exacerbation. In this context, medicinal plants such as Amburana cearensis appear as a potential source of new drugs for the treatment of exacerbated allergic asthma. Faced with the risk of extinction of this wild species, in the last years several chemical and pharmacological studies have been carried out generating promising results with cultivated species, which has as active principles coumarin (CM) and vanillic acid (AV). The aim of this study was to investigate the effects of the standardized extract of cultured A. cearensis (ESPACC, markers: CM and AV), CM and AV on exacerbated allergic asthma in BALB / c mice, including the evaluation of these in the neutrophilic response. The pattern of allergic asthma induced by OVA and exacerbated by LPS in BALB / c mice was investigated, investigating different experimental conditions that were evaluated mainly by the analysis of the accumulation of inflammatory cells in the bronchoalveolar lavage (BAL) of the animals. The effects of ESPACC and CM (vo or ip) on the accumulation of inflammatory cells, tissue morphology and levels of IL-4 and TNF-α cytokines in BAL of animals sensitized and challenged with LPS + OVA , in addition to the evaluation of the effects of ESPACC, CM and AV on the degranulation and production of reactive oxygen species (EROS) in PMA-activated neutrophils. In the standardization of the exacerbated asthma model, it was seen that the dose of OVA and LPS, as well as the increase in the duration of exposure to the antigens, were determinant for obtaining the model of exacerbated allergic asthma. Treatment of CM animals (10 or 20 mg / kg, ip or v0, respectively) did not significantly reduce leukocyte accumulation in BAL compared to the control group, but selectively modulated neutrophil migration. ESPACC (100 mg / kg, ip) was able to significantly inhibit leukocyte accumulation in BAL, mucus production and cytokine secretion. In neutrophil culture, ESPACC, CM and AV significantly reduced the neutrophil degranulation induced by PMA measured by the release of MPO, as well as EROS production. The results indicate that cultured A. cearensis, CM and AV have an anti-inflammatory effect in an exacerbated allergic asthma model, modulating inflammatory cell accumulation and neutrophil response, as well as the production of mucus, cytokines and EROS. The results showed that cumaru and its chemical constituents are a potential source for the development of anti-inflammatory drugs to be used in the treatment of exacerbated allergic asthma.A asma é uma doença inflamatória crônica que afeta mais de 300 milhões de pessoas ao redor do mundo. A principal causa de internação e mortalidade relacionadas a doença são as exacerbações caracterizadas principalmente por um perfil de resposta inflamatória onde os linfócitos Th2, Th17 e neutrófilos têm um papel importante, além da resistência à terapia com corticoides. Isso demonstra a importância de pesquisas de novos fármacos para o tratamento da asma alérgica, em especial a exacerbada. Nesse contexto, as plantas medicinais como Amburana cearensis surgem como fonte em potencial de novos fármacos para o tratamento da asma alérgica exacerbada. Considerando o risco de extinção da planta silvestre, nos últimos anos diversos estudos químicos e farmacológicos têm sido realizados gerando resultados promissores com espécie cultivada, que possui como princípios ativos a cumarina (CM) e ácido vanílico (AV). Diante do exposto, o objetivo do presente estudo foi investigar os efeitos do extrato seco padronizado de A. cearensis cultivada (ESPACC, marcadores: CM e AV), CM e AV sobre a asma alérgica exacerbada em camundongos BALB/c, incluindo a avaliação desses na resposta neutrofílica. Foi realizada a padronização do modelo de asma alérgica induzida por OVA e exacerbada por LPS em camundongos BALB/c, investigando diferentes condições experimentais que foram avaliadas principalmente pela análise do acúmulo de células inflamatórias no lavado broncoalveolar (LBA) dos animais. A seguir, foram avaliados os efeitos do ESPACC e CM (vo ou ip) sobre o acúmulo de células inflamatórias, a morfologia do tecido e os níveis de citocinas IL-4 e TNF-α no LBA de animais sensibilizados e desafiados com LPS+OVA, além da avaliação dos efeitos do ESPACC, CM e AV sobre a desgranulação e produção de espécies reativas de oxigênio (EROS) em neutrófilos ativados por PMA. Na padronização do modelo de asma exacerbada, foi visto que a dose de OVA e LPS, bem como o aumento no tempo de duração da exposição aos antígenos foram determinanantes para a obtenção do modelo de asma alérgica exacerbada. O tratamento dos animais com CM (10 ou 20 mg/kg, via ip ou vo, respectivamente) não reduziu significativamente o acúmulo de leucócitos no LBA em relação ao grupo controle, mas modulou seletivamente a migração de neutrófilos. O ESPACC (100 mg/kg, ip) foi capaz de inibir significativamente o acúmulo de leucócitos no LBA, a produção de muco e a secreção de citocinas. Em cultura de neutrófilos, ESPACC, CM e AV reduziram significativamente a desgranulação de neutrófilos induzida por PMA mensurada pela liberação de MPO, bem como a produção de EROS. Os resultados indicam que A. cearensis cultivada, CM e AV possuem efeito anti-inflamatório em modelo de asma alérgica exacerbada, modulando o acúmulo de células inflamatória e a resposta neutrofílica, bem a produção de muco, citocinas e EROS. Os resultados obtidos mostraram que o cumaru e seus constituintes químicos constituem uma fonte em potencial para o desenvolvimento de fármacos anti-inflamatórios a serem empregados no tratamento da asma alérgica exacerbada.Leal, Luzia Kalyne Almeida MoreiraAmaral, Hilmara Helia de Sousa2017-12-18T13:41:18Z2017-12-18T13:41:18Z2017-12-04info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfAMARAL, H. H. S. Extrato seco padronizado de Amburana cearensis cultivada e constituintes químicos modulam a inflamação em um novo modelo de asma exacerbada em camundongos BALB/C e a resposta neutrofílica in vitro. 2017. 110 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2017.http://www.repositorio.ufc.br/handle/riufc/28570porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2019-10-17T12:55:55Zoai:repositorio.ufc.br:riufc/28570Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T18:27:50.820417Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Extrato seco padronizado de Amburana cearensis cultivada e constituintes químicos modulam a inflamação em um novo modelo de asma exacerbada em camundongos BALB/C e a resposta neutrofílica in vitro
Amburana cearensis cultivated standard dried extract and chemical constituents modulate inflammation in a new exacerbated asthma model in mice BALB/C and in vitro neutrophilic response
title Extrato seco padronizado de Amburana cearensis cultivada e constituintes químicos modulam a inflamação em um novo modelo de asma exacerbada em camundongos BALB/C e a resposta neutrofílica in vitro
spellingShingle Extrato seco padronizado de Amburana cearensis cultivada e constituintes químicos modulam a inflamação em um novo modelo de asma exacerbada em camundongos BALB/C e a resposta neutrofílica in vitro
Amaral, Hilmara Helia de Sousa
Asma
Ácido Vanílico
Farmacologia
title_short Extrato seco padronizado de Amburana cearensis cultivada e constituintes químicos modulam a inflamação em um novo modelo de asma exacerbada em camundongos BALB/C e a resposta neutrofílica in vitro
title_full Extrato seco padronizado de Amburana cearensis cultivada e constituintes químicos modulam a inflamação em um novo modelo de asma exacerbada em camundongos BALB/C e a resposta neutrofílica in vitro
title_fullStr Extrato seco padronizado de Amburana cearensis cultivada e constituintes químicos modulam a inflamação em um novo modelo de asma exacerbada em camundongos BALB/C e a resposta neutrofílica in vitro
title_full_unstemmed Extrato seco padronizado de Amburana cearensis cultivada e constituintes químicos modulam a inflamação em um novo modelo de asma exacerbada em camundongos BALB/C e a resposta neutrofílica in vitro
title_sort Extrato seco padronizado de Amburana cearensis cultivada e constituintes químicos modulam a inflamação em um novo modelo de asma exacerbada em camundongos BALB/C e a resposta neutrofílica in vitro
author Amaral, Hilmara Helia de Sousa
author_facet Amaral, Hilmara Helia de Sousa
author_role author
dc.contributor.none.fl_str_mv Leal, Luzia Kalyne Almeida Moreira
dc.contributor.author.fl_str_mv Amaral, Hilmara Helia de Sousa
dc.subject.por.fl_str_mv Asma
Ácido Vanílico
Farmacologia
topic Asma
Ácido Vanílico
Farmacologia
description Asthma is a chronic inflammatory disease that affects more than 300 million people around the world. The main cause of hospitalization and mortality related to the disease are the exacerbations characterized mainly by an inflammatory response profile where Th2, Th17 and neutrophil lymphocytes play an important role in addition to resistance to corticosteroid therapy. This justifies the importance of research on new drugs for the treatment of allergic asthma, especially exacerbation. In this context, medicinal plants such as Amburana cearensis appear as a potential source of new drugs for the treatment of exacerbated allergic asthma. Faced with the risk of extinction of this wild species, in the last years several chemical and pharmacological studies have been carried out generating promising results with cultivated species, which has as active principles coumarin (CM) and vanillic acid (AV). The aim of this study was to investigate the effects of the standardized extract of cultured A. cearensis (ESPACC, markers: CM and AV), CM and AV on exacerbated allergic asthma in BALB / c mice, including the evaluation of these in the neutrophilic response. The pattern of allergic asthma induced by OVA and exacerbated by LPS in BALB / c mice was investigated, investigating different experimental conditions that were evaluated mainly by the analysis of the accumulation of inflammatory cells in the bronchoalveolar lavage (BAL) of the animals. The effects of ESPACC and CM (vo or ip) on the accumulation of inflammatory cells, tissue morphology and levels of IL-4 and TNF-α cytokines in BAL of animals sensitized and challenged with LPS + OVA , in addition to the evaluation of the effects of ESPACC, CM and AV on the degranulation and production of reactive oxygen species (EROS) in PMA-activated neutrophils. In the standardization of the exacerbated asthma model, it was seen that the dose of OVA and LPS, as well as the increase in the duration of exposure to the antigens, were determinant for obtaining the model of exacerbated allergic asthma. Treatment of CM animals (10 or 20 mg / kg, ip or v0, respectively) did not significantly reduce leukocyte accumulation in BAL compared to the control group, but selectively modulated neutrophil migration. ESPACC (100 mg / kg, ip) was able to significantly inhibit leukocyte accumulation in BAL, mucus production and cytokine secretion. In neutrophil culture, ESPACC, CM and AV significantly reduced the neutrophil degranulation induced by PMA measured by the release of MPO, as well as EROS production. The results indicate that cultured A. cearensis, CM and AV have an anti-inflammatory effect in an exacerbated allergic asthma model, modulating inflammatory cell accumulation and neutrophil response, as well as the production of mucus, cytokines and EROS. The results showed that cumaru and its chemical constituents are a potential source for the development of anti-inflammatory drugs to be used in the treatment of exacerbated allergic asthma.
publishDate 2017
dc.date.none.fl_str_mv 2017-12-18T13:41:18Z
2017-12-18T13:41:18Z
2017-12-04
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
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dc.identifier.uri.fl_str_mv AMARAL, H. H. S. Extrato seco padronizado de Amburana cearensis cultivada e constituintes químicos modulam a inflamação em um novo modelo de asma exacerbada em camundongos BALB/C e a resposta neutrofílica in vitro. 2017. 110 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2017.
http://www.repositorio.ufc.br/handle/riufc/28570
identifier_str_mv AMARAL, H. H. S. Extrato seco padronizado de Amburana cearensis cultivada e constituintes químicos modulam a inflamação em um novo modelo de asma exacerbada em camundongos BALB/C e a resposta neutrofílica in vitro. 2017. 110 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2017.
url http://www.repositorio.ufc.br/handle/riufc/28570
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