Avaliação das atividades tripanocida, leishmanicida e imunomoduladora de extratos de sementes de Lonchocarpus cultratus

Detalhes bibliográficos
Ano de defesa: 2020
Autor(a) principal: Banhuk, Fernanda Weyand lattes
Orientador(a): Menolli, Rafael Andrade lattes
Banca de defesa: Menolli, Rafael Andrade lattes, Lovo Martins, Maria Isabel lattes, Bueno, Fernanda Giacomini lattes
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Estadual do Oeste do Paraná
Cascavel
Programa de Pós-Graduação: Programa de Pós-Graduação em Ciências Farmacêuticas
Departamento: Centro de Ciências Médicas e Farmacêuticas
País: Brasil
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: http://tede.unioeste.br/handle/tede/5069
Resumo: Chagas disease and leishmaniasis expose the need for searching more effective and safer new medicinal drugs. To broaden the knowledge about cytotoxicity and the potential of plant species is of utmost importance to obtain new therapeutic options. Plants of the genus Lonchocarpus have high medicinal potential due to the wide variety of bioactive components, presenting different biological activities, including trypanocidal and leishmanicidal activities. Lonchocarpus cultratus (L. cultratus) species features chalcones as lonchocarpine and isocordoin, steroids, and terpenes. The lack of studies on antiparasitic activity has propeled this research to investigate cytotoxicity, the action on the immunomodulation of macrophages, and the response against two parasites: Trypanosoma cruzi (T. cruzi) and Leishmania amazonensis (L. amazonensis). The extracts were obtained from the seeds of L. cultratus in vitro, focusing on in vivo use. When evaluated by the colorimetric methodology of reducing MTT tetrazolium salt to formazan, the hexanic and methanolic extracts of L. cultratus (LHS and LMS respectively) did not show cytotoxicity in murine macrophages. The dichloromethane extract of L. cultratus (LDS) was cytotoxic at the highest concentrations. The three extracts neither stimulate the release of nitric oxide nor inhibit it in macrophages under lipopolysaccharide (LPS) stimuli. The LDS and LMS extracts presented the highest activity against the tested T. cruzi forms, in their highest concentrations, with values close to those observed for Benzonidazole, used for the treatment of Chagas disease. The three extracts showed significant activity on the infection rate of T. cruzi amastigotes. The LDS and LHS extracts were the most active against the promastigote and amastigote forms of L. amazonensis, with values close to that found for Glucantime®, a positive treatment control. LDS showed low rates of selectivity for both parasites, as it was cytotoxic to murine macrophages. The three extracts did not stimulate the release of interleukin 1-beta and interleukin 10 (IL-1β and IL-10, respectively). Since they did not alter the release of NO, they may have exerted direct antiparasitic activity on parasites. There is a need to perform more in-depth tests to know the mechanisms by which the extracts exercise these actions, in order to obtain a potential therapeutic alternative for the pathologies treated in this study.
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spelling Menolli, Rafael Andradehttp://lattes.cnpq.br/2119646769798898Ayala, Thais Sopranihttp://lattes.cnpq.br/5576750114963342Menolli, Rafael Andradehttp://lattes.cnpq.br/2119646769798898Lovo Martins, Maria Isabelhttp://lattes.cnpq.br/7132608955863120Bueno, Fernanda Giacominihttp://lattes.cnpq.br/2735821835018618http://lattes.cnpq.br/8532752534015486Banhuk, Fernanda Weyand2020-10-27T16:49:24Z2020-03-02BANHUK, Fernanda Weyand. Avaliação das atividades tripanocida, leishmanicida e imunomoduladora de extratos de sementes de Lonchocarpus cultratus. 2020. 77 f. Dissertação (Programa de Pós-Graduação em Ciências Farmacêuticas) - Universidade Estadual do Oeste do Paraná, Cascavel - PR.http://tede.unioeste.br/handle/tede/5069Chagas disease and leishmaniasis expose the need for searching more effective and safer new medicinal drugs. To broaden the knowledge about cytotoxicity and the potential of plant species is of utmost importance to obtain new therapeutic options. Plants of the genus Lonchocarpus have high medicinal potential due to the wide variety of bioactive components, presenting different biological activities, including trypanocidal and leishmanicidal activities. Lonchocarpus cultratus (L. cultratus) species features chalcones as lonchocarpine and isocordoin, steroids, and terpenes. The lack of studies on antiparasitic activity has propeled this research to investigate cytotoxicity, the action on the immunomodulation of macrophages, and the response against two parasites: Trypanosoma cruzi (T. cruzi) and Leishmania amazonensis (L. amazonensis). The extracts were obtained from the seeds of L. cultratus in vitro, focusing on in vivo use. When evaluated by the colorimetric methodology of reducing MTT tetrazolium salt to formazan, the hexanic and methanolic extracts of L. cultratus (LHS and LMS respectively) did not show cytotoxicity in murine macrophages. The dichloromethane extract of L. cultratus (LDS) was cytotoxic at the highest concentrations. The three extracts neither stimulate the release of nitric oxide nor inhibit it in macrophages under lipopolysaccharide (LPS) stimuli. The LDS and LMS extracts presented the highest activity against the tested T. cruzi forms, in their highest concentrations, with values close to those observed for Benzonidazole, used for the treatment of Chagas disease. The three extracts showed significant activity on the infection rate of T. cruzi amastigotes. The LDS and LHS extracts were the most active against the promastigote and amastigote forms of L. amazonensis, with values close to that found for Glucantime®, a positive treatment control. LDS showed low rates of selectivity for both parasites, as it was cytotoxic to murine macrophages. The three extracts did not stimulate the release of interleukin 1-beta and interleukin 10 (IL-1β and IL-10, respectively). Since they did not alter the release of NO, they may have exerted direct antiparasitic activity on parasites. There is a need to perform more in-depth tests to know the mechanisms by which the extracts exercise these actions, in order to obtain a potential therapeutic alternative for the pathologies treated in this study.A doença de Chagas e a leishmaniose mostram a necessidade constante da busca de novos medicamentos que sejam mais eficientes e seguros para o tratamento. Ampliar o conhecimento acerca da citotoxicidade e do potencial de espécies vegetais é de fundamental importância, a fim de se obter novas opções terapêuticas. As plantas do gênero Lonchocarpus estão dentre as plantas com alto potencial medicinal devido à grande variedade de componentes bioativos, apresentando diferentes atividades biológicas, incluindo as atividades tripanocida e leishmanicida. A espécie Lonchocarpus cultratus (L. cultratus) apresenta em sua composição chalconas, como a lonchocarpina e a isocordoína, esteroides e terpenos. Por não existirem muitos trabalhos a respeito da sua atividade antiparasitária, o presente trabalho teve como objetivo investigar a citotoxicidade e a ação sobre a imunomodulação dos macrófagos e contra os parasitas Trypanosoma cruzi (T. cruzi) e Leishmania amazonensis (L. amazonensis) de extratos obtidos das sementes de L. cultratus in vitro, visando seu uso in vivo. Quando avaliados pela metodologia colorimétrica de redução do sal de tetrazolium MTT à formazan, os extratos hexânico e metanólico de L. cultratus (LHS e LMS, respectivamente) não apresentaram citotoxicidade em macrófagos murinos e o extrato diclorometânico de L. cultratus (LDS) foi citotóxico nas concentrações mais altas. Os três extratos não estimularam a liberação de óxido nítrico, nem inibiram essa liberação em macrófagos estimulados por lipopolissacarídeo (LPS). Os extratos LDS e LMS foram os que apresentaram maior atividade contra as formas T. cruzi testadas, em suas concentrações mais altas, com valores próximos ao observado pelo Benzonidazol, medicamento utilizado no tratamento da doença de Chagas. Os três extratos apresentaram atividade significativa sobre o índice de internalização de amastigotas de T. cruzi. Os extratos LDS e LHS foram os que se apresentaram mais ativos contra as formas promastigotas e amastigotas de L. amazonensis, com valores próximos do encontrado para o Glucantime®, controle positivo de tratamento. Por ter sido citotóxico para os macrófagos murinos, o LDS apresentou baixos índices de seletividade para ambos os parasitas. Os três extratos não estimularam a liberação da interleucina 1-beta e da interleucina 10 (IL-1β e IL-10, respectivamente) e, uma vez que não alteraram a liberação de NO, sugere-se que exerceram atividade antiparasitária direta sobre os parasitas. Há a necessidade da realização de ensaios mais aprofundados e de buscar conhecer os mecanismos pelos quais os extratos exercem essas ações, a fim de se obter uma alternativa terapêutica potencial para as patologias tratadas neste estudo.Submitted by Neusa Fagundes (neusa.fagundes@unioeste.br) on 2020-10-27T16:49:24Z No. of bitstreams: 2 Fernanda_Banhuk2020.pdf: 1030466 bytes, checksum: 1f959e4ba2a7508ef8208bff66323c04 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2020-10-27T16:49:24Z (GMT). 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dc.title.por.fl_str_mv Avaliação das atividades tripanocida, leishmanicida e imunomoduladora de extratos de sementes de Lonchocarpus cultratus
dc.title.alternative.eng.fl_str_mv Evaluation of tripanocidal, leishmanicidal and immunomodulatory activities of Lonchocarpus cultratus seed extracts
title Avaliação das atividades tripanocida, leishmanicida e imunomoduladora de extratos de sementes de Lonchocarpus cultratus
spellingShingle Avaliação das atividades tripanocida, leishmanicida e imunomoduladora de extratos de sementes de Lonchocarpus cultratus
Banhuk, Fernanda Weyand
Doença de Chagas
Leishmanioses
Extratos naturais
Atividade anti-T.cruzi
Atividade anti-Leishmania
Chagas disease
Leishmaniasis
Natural extracts
Anti-T.cruzi activity
Anti-Leishmania activity
CIENCIAS DA SAUDE::FARMACIA
title_short Avaliação das atividades tripanocida, leishmanicida e imunomoduladora de extratos de sementes de Lonchocarpus cultratus
title_full Avaliação das atividades tripanocida, leishmanicida e imunomoduladora de extratos de sementes de Lonchocarpus cultratus
title_fullStr Avaliação das atividades tripanocida, leishmanicida e imunomoduladora de extratos de sementes de Lonchocarpus cultratus
title_full_unstemmed Avaliação das atividades tripanocida, leishmanicida e imunomoduladora de extratos de sementes de Lonchocarpus cultratus
title_sort Avaliação das atividades tripanocida, leishmanicida e imunomoduladora de extratos de sementes de Lonchocarpus cultratus
author Banhuk, Fernanda Weyand
author_facet Banhuk, Fernanda Weyand
author_role author
dc.contributor.advisor1.fl_str_mv Menolli, Rafael Andrade
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/2119646769798898
dc.contributor.advisor-co1.fl_str_mv Ayala, Thais Soprani
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/5576750114963342
dc.contributor.referee1.fl_str_mv Menolli, Rafael Andrade
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/2119646769798898
dc.contributor.referee2.fl_str_mv Lovo Martins, Maria Isabel
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/7132608955863120
dc.contributor.referee3.fl_str_mv Bueno, Fernanda Giacomini
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/2735821835018618
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/8532752534015486
dc.contributor.author.fl_str_mv Banhuk, Fernanda Weyand
contributor_str_mv Menolli, Rafael Andrade
Ayala, Thais Soprani
Menolli, Rafael Andrade
Lovo Martins, Maria Isabel
Bueno, Fernanda Giacomini
dc.subject.por.fl_str_mv Doença de Chagas
Leishmanioses
Extratos naturais
Atividade anti-T.cruzi
Atividade anti-Leishmania
topic Doença de Chagas
Leishmanioses
Extratos naturais
Atividade anti-T.cruzi
Atividade anti-Leishmania
Chagas disease
Leishmaniasis
Natural extracts
Anti-T.cruzi activity
Anti-Leishmania activity
CIENCIAS DA SAUDE::FARMACIA
dc.subject.eng.fl_str_mv Chagas disease
Leishmaniasis
Natural extracts
Anti-T.cruzi activity
Anti-Leishmania activity
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE::FARMACIA
description Chagas disease and leishmaniasis expose the need for searching more effective and safer new medicinal drugs. To broaden the knowledge about cytotoxicity and the potential of plant species is of utmost importance to obtain new therapeutic options. Plants of the genus Lonchocarpus have high medicinal potential due to the wide variety of bioactive components, presenting different biological activities, including trypanocidal and leishmanicidal activities. Lonchocarpus cultratus (L. cultratus) species features chalcones as lonchocarpine and isocordoin, steroids, and terpenes. The lack of studies on antiparasitic activity has propeled this research to investigate cytotoxicity, the action on the immunomodulation of macrophages, and the response against two parasites: Trypanosoma cruzi (T. cruzi) and Leishmania amazonensis (L. amazonensis). The extracts were obtained from the seeds of L. cultratus in vitro, focusing on in vivo use. When evaluated by the colorimetric methodology of reducing MTT tetrazolium salt to formazan, the hexanic and methanolic extracts of L. cultratus (LHS and LMS respectively) did not show cytotoxicity in murine macrophages. The dichloromethane extract of L. cultratus (LDS) was cytotoxic at the highest concentrations. The three extracts neither stimulate the release of nitric oxide nor inhibit it in macrophages under lipopolysaccharide (LPS) stimuli. The LDS and LMS extracts presented the highest activity against the tested T. cruzi forms, in their highest concentrations, with values close to those observed for Benzonidazole, used for the treatment of Chagas disease. The three extracts showed significant activity on the infection rate of T. cruzi amastigotes. The LDS and LHS extracts were the most active against the promastigote and amastigote forms of L. amazonensis, with values close to that found for Glucantime®, a positive treatment control. LDS showed low rates of selectivity for both parasites, as it was cytotoxic to murine macrophages. The three extracts did not stimulate the release of interleukin 1-beta and interleukin 10 (IL-1β and IL-10, respectively). Since they did not alter the release of NO, they may have exerted direct antiparasitic activity on parasites. There is a need to perform more in-depth tests to know the mechanisms by which the extracts exercise these actions, in order to obtain a potential therapeutic alternative for the pathologies treated in this study.
publishDate 2020
dc.date.accessioned.fl_str_mv 2020-10-27T16:49:24Z
dc.date.issued.fl_str_mv 2020-03-02
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv BANHUK, Fernanda Weyand. Avaliação das atividades tripanocida, leishmanicida e imunomoduladora de extratos de sementes de Lonchocarpus cultratus. 2020. 77 f. Dissertação (Programa de Pós-Graduação em Ciências Farmacêuticas) - Universidade Estadual do Oeste do Paraná, Cascavel - PR.
dc.identifier.uri.fl_str_mv http://tede.unioeste.br/handle/tede/5069
identifier_str_mv BANHUK, Fernanda Weyand. Avaliação das atividades tripanocida, leishmanicida e imunomoduladora de extratos de sementes de Lonchocarpus cultratus. 2020. 77 f. Dissertação (Programa de Pós-Graduação em Ciências Farmacêuticas) - Universidade Estadual do Oeste do Paraná, Cascavel - PR.
url http://tede.unioeste.br/handle/tede/5069
dc.language.iso.fl_str_mv por
language por
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dc.relation.confidence.fl_str_mv 600
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dc.relation.department.fl_str_mv -8940439713387849267
dc.relation.cnpq.fl_str_mv 6997636413449754996
dc.relation.sponsorship.fl_str_mv 2075167498588264571
dc.rights.driver.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
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