In vitro and in vivo antileishmanial activity of b-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis.
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFOP |
Texto Completo: | http://www.repositorio.ufop.br/jspui/handle/123456789/13834 https://doi.org/10.1051/parasite/2021036 |
Resumo: | Current treatments of visceral leishmaniasis face limitations due to drug side effects and/or high cost, along with the emergence of parasite resistance. Novel and low-cost antileishmanial agents are therefore required. We report herein the antileishmanial activity of b-acetyl-digitoxin (b-AD), a cardenolide isolated from Digitalis lanata leaves, assayed in vitro and in vivo against Leishmania infantum. Results showed direct action of b-AD against parasites, as well as efficacy for the treatment of Leishmania-infected macrophages. In vivo experiments using b-AD-containing Pluronic F127 polymeric micelles (b-AD/Mic) to treat L. infantum-infected mice showed that this composition reduced the parasite load in distinct organs in more significant levels. It also induced the development of anti-parasite Th1-type immunity, attested by high levels of IFN-c, IL-12, TNF-a, GM-CSF, nitrite and specific IgG2a antibodies, in addition to low IL-4 and IL-10 contents, along with higher IFN-c-producing CD4+ and CD8+ T-cell frequency. Furthermore, low toxicity was found in the organs of the treated animals. Comparing the therapeutic effect between the treatments, b-AD/Mic was the most effective in protecting animals against infection, when compared to the other groups including miltefosine used as a drug control. Data found 15 days after treatment were similar to those obtained one day post-therapy. In conclusion, the results obtained suggest that b-AD/Mic is a promising antileishmanial agent and deserves further studies to investigate its potential to treat visceral leishmaniasis. |
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In vitro and in vivo antileishmanial activity of b-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis.Activité antileishmaniale in vitro et in vivo de la b-acétyl-digitoxine, un cardénolide de Digitalis lanata potentiellement utile pour traiter la leishmaniose viscérale.Drug repositioningToxicityMiltefosineCurrent treatments of visceral leishmaniasis face limitations due to drug side effects and/or high cost, along with the emergence of parasite resistance. Novel and low-cost antileishmanial agents are therefore required. We report herein the antileishmanial activity of b-acetyl-digitoxin (b-AD), a cardenolide isolated from Digitalis lanata leaves, assayed in vitro and in vivo against Leishmania infantum. Results showed direct action of b-AD against parasites, as well as efficacy for the treatment of Leishmania-infected macrophages. In vivo experiments using b-AD-containing Pluronic F127 polymeric micelles (b-AD/Mic) to treat L. infantum-infected mice showed that this composition reduced the parasite load in distinct organs in more significant levels. It also induced the development of anti-parasite Th1-type immunity, attested by high levels of IFN-c, IL-12, TNF-a, GM-CSF, nitrite and specific IgG2a antibodies, in addition to low IL-4 and IL-10 contents, along with higher IFN-c-producing CD4+ and CD8+ T-cell frequency. Furthermore, low toxicity was found in the organs of the treated animals. Comparing the therapeutic effect between the treatments, b-AD/Mic was the most effective in protecting animals against infection, when compared to the other groups including miltefosine used as a drug control. Data found 15 days after treatment were similar to those obtained one day post-therapy. In conclusion, the results obtained suggest that b-AD/Mic is a promising antileishmanial agent and deserves further studies to investigate its potential to treat visceral leishmaniasis.Les traitements actuels de la leishmaniose viscérale font face à des limitations dues aux effets secondaires des médicaments et/ou à leur coût élevé, ainsi qu’à l’émergence d’une résistance parasitaire. Des agents antileishmaniaux nouveaux et peu coûteux sont donc nécessaires. Nous rapportons ici l’activité antileishmaniale de la b-acétyl-digitoxine (b-AD), un cardénolide isolé à partir de feuilles de Digitalis lanata, mesurée in vitro et in vivo contre Leishmania infantum. Les résultats ont montré une action directe de la b-AD contre les parasites, ainsi qu’une efficacité pour le traitement des macrophages infectés par Leishmania. Des expériences in vivo utilisant des micelles polymériques Pluronic F127 contenant de la b-AD (b-AD/Mic) pour traiter des souris infectées par L. infantum ont montré que cette composition réduisait à des niveaux plus significatifs la charge parasitaire dans différents organes, ainsi que le développement d’une immunité antiparasitaire de type Th1, attestée par les taux élevés d’IFN-c, d’IL-12, de TNF-a, de GM-CSF, de nitrite et d’anticorps IgG2a spécifiques, en plus des faibles taux d’IL-4 et IL-10, ainsi qu’une fréquence plus élevée des cellules T CD4+ and CD8+ productrices d’ IFN-c. De plus, une faible toxicité a été trouvée dans les organes des animaux traités. En comparant l’effet thérapeutique des traitements, b-AD/Mic était le plus efficace pour protéger les animaux contre l’infection, par rapport aux autres groupes comprenant la miltefosine utilisée comme contrôle médicamenteux. Les données trouvées 15 jours après le traitement étaient similaires à celles obtenues un jour après le traitement. En conclusion, les résultats obtenus suggèrent que b-AD/Mic est un agent antileishmanial prometteur et mérite des études supplémentaires pour étudier son potentiel à traiter la leishmaniose viscérale.2021-09-30T17:29:28Z2021-09-30T17:29:28Z2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfFREITAS, C. S. de et al. In vitro and in vivo antileishmanial activity of b-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis. Parasite, v. 28, artigo 38, abr. 2021. Disponível em: <https://www.parasite-journal.org/articles/parasite/full_html/2021/01/parasite200128/parasite200128.html>. Acesso em: 10 jun. 2021.1776-1042http://www.repositorio.ufop.br/jspui/handle/123456789/13834https://doi.org/10.1051/parasite/2021036This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Fonte: o PDF do artigo.info:eu-repo/semantics/openAccessFreitas, Camila Simões deLage, Daniela PagliaraSilva, João Augusto Oliveira daCosta, Rafaella RodriguesMendonça, Débora Vasconcelos CostaMartins, Vívian TamiettiReis, Thiago Alves Rosa dosAntinarelli, Luciana Maria RibeiroMachado, Amanda SanchezTavares, Grasiele de Sousa VieiraRamos, Fernanda FonsecaBrito, Rory Cristiane Fortes deRibeiro, Fernanda LudolfChávez Fumagalli, Miguel AngelRoatt, Bruno MendesRamos, Gabriela S.Munkert, JenniferOttoni, Flaviano MeloCampana, Priscilla Rodrigues ValadaresDuarte, Mariana CostaGonçalves, Denise UtschCoimbra, Elaine SoaresBraga, Fernão CastroPádua, Rodrigo Maia deCoelho, Eduardo Antônio Ferrazengreponame:Repositório Institucional da UFOPinstname:Universidade Federal de Ouro Preto (UFOP)instacron:UFOP2024-01-31T17:56:16Zoai:repositorio.ufop.br:123456789/13834Repositório InstitucionalPUBhttp://www.repositorio.ufop.br/oai/requestrepositorio@ufop.edu.bropendoar:32332024-01-31T17:56:16Repositório Institucional da UFOP - Universidade Federal de Ouro Preto (UFOP)false |
dc.title.none.fl_str_mv |
In vitro and in vivo antileishmanial activity of b-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis. Activité antileishmaniale in vitro et in vivo de la b-acétyl-digitoxine, un cardénolide de Digitalis lanata potentiellement utile pour traiter la leishmaniose viscérale. |
title |
In vitro and in vivo antileishmanial activity of b-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis. |
spellingShingle |
In vitro and in vivo antileishmanial activity of b-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis. Freitas, Camila Simões de Drug repositioning Toxicity Miltefosine |
title_short |
In vitro and in vivo antileishmanial activity of b-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis. |
title_full |
In vitro and in vivo antileishmanial activity of b-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis. |
title_fullStr |
In vitro and in vivo antileishmanial activity of b-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis. |
title_full_unstemmed |
In vitro and in vivo antileishmanial activity of b-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis. |
title_sort |
In vitro and in vivo antileishmanial activity of b-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis. |
author |
Freitas, Camila Simões de |
author_facet |
Freitas, Camila Simões de Lage, Daniela Pagliara Silva, João Augusto Oliveira da Costa, Rafaella Rodrigues Mendonça, Débora Vasconcelos Costa Martins, Vívian Tamietti Reis, Thiago Alves Rosa dos Antinarelli, Luciana Maria Ribeiro Machado, Amanda Sanchez Tavares, Grasiele de Sousa Vieira Ramos, Fernanda Fonseca Brito, Rory Cristiane Fortes de Ribeiro, Fernanda Ludolf Chávez Fumagalli, Miguel Angel Roatt, Bruno Mendes Ramos, Gabriela S. Munkert, Jennifer Ottoni, Flaviano Melo Campana, Priscilla Rodrigues Valadares Duarte, Mariana Costa Gonçalves, Denise Utsch Coimbra, Elaine Soares Braga, Fernão Castro Pádua, Rodrigo Maia de Coelho, Eduardo Antônio Ferraz |
author_role |
author |
author2 |
Lage, Daniela Pagliara Silva, João Augusto Oliveira da Costa, Rafaella Rodrigues Mendonça, Débora Vasconcelos Costa Martins, Vívian Tamietti Reis, Thiago Alves Rosa dos Antinarelli, Luciana Maria Ribeiro Machado, Amanda Sanchez Tavares, Grasiele de Sousa Vieira Ramos, Fernanda Fonseca Brito, Rory Cristiane Fortes de Ribeiro, Fernanda Ludolf Chávez Fumagalli, Miguel Angel Roatt, Bruno Mendes Ramos, Gabriela S. Munkert, Jennifer Ottoni, Flaviano Melo Campana, Priscilla Rodrigues Valadares Duarte, Mariana Costa Gonçalves, Denise Utsch Coimbra, Elaine Soares Braga, Fernão Castro Pádua, Rodrigo Maia de Coelho, Eduardo Antônio Ferraz |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Freitas, Camila Simões de Lage, Daniela Pagliara Silva, João Augusto Oliveira da Costa, Rafaella Rodrigues Mendonça, Débora Vasconcelos Costa Martins, Vívian Tamietti Reis, Thiago Alves Rosa dos Antinarelli, Luciana Maria Ribeiro Machado, Amanda Sanchez Tavares, Grasiele de Sousa Vieira Ramos, Fernanda Fonseca Brito, Rory Cristiane Fortes de Ribeiro, Fernanda Ludolf Chávez Fumagalli, Miguel Angel Roatt, Bruno Mendes Ramos, Gabriela S. Munkert, Jennifer Ottoni, Flaviano Melo Campana, Priscilla Rodrigues Valadares Duarte, Mariana Costa Gonçalves, Denise Utsch Coimbra, Elaine Soares Braga, Fernão Castro Pádua, Rodrigo Maia de Coelho, Eduardo Antônio Ferraz |
dc.subject.por.fl_str_mv |
Drug repositioning Toxicity Miltefosine |
topic |
Drug repositioning Toxicity Miltefosine |
description |
Current treatments of visceral leishmaniasis face limitations due to drug side effects and/or high cost, along with the emergence of parasite resistance. Novel and low-cost antileishmanial agents are therefore required. We report herein the antileishmanial activity of b-acetyl-digitoxin (b-AD), a cardenolide isolated from Digitalis lanata leaves, assayed in vitro and in vivo against Leishmania infantum. Results showed direct action of b-AD against parasites, as well as efficacy for the treatment of Leishmania-infected macrophages. In vivo experiments using b-AD-containing Pluronic F127 polymeric micelles (b-AD/Mic) to treat L. infantum-infected mice showed that this composition reduced the parasite load in distinct organs in more significant levels. It also induced the development of anti-parasite Th1-type immunity, attested by high levels of IFN-c, IL-12, TNF-a, GM-CSF, nitrite and specific IgG2a antibodies, in addition to low IL-4 and IL-10 contents, along with higher IFN-c-producing CD4+ and CD8+ T-cell frequency. Furthermore, low toxicity was found in the organs of the treated animals. Comparing the therapeutic effect between the treatments, b-AD/Mic was the most effective in protecting animals against infection, when compared to the other groups including miltefosine used as a drug control. Data found 15 days after treatment were similar to those obtained one day post-therapy. In conclusion, the results obtained suggest that b-AD/Mic is a promising antileishmanial agent and deserves further studies to investigate its potential to treat visceral leishmaniasis. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-09-30T17:29:28Z 2021-09-30T17:29:28Z 2021 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
FREITAS, C. S. de et al. In vitro and in vivo antileishmanial activity of b-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis. Parasite, v. 28, artigo 38, abr. 2021. Disponível em: <https://www.parasite-journal.org/articles/parasite/full_html/2021/01/parasite200128/parasite200128.html>. Acesso em: 10 jun. 2021. 1776-1042 http://www.repositorio.ufop.br/jspui/handle/123456789/13834 https://doi.org/10.1051/parasite/2021036 |
identifier_str_mv |
FREITAS, C. S. de et al. In vitro and in vivo antileishmanial activity of b-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis. Parasite, v. 28, artigo 38, abr. 2021. Disponível em: <https://www.parasite-journal.org/articles/parasite/full_html/2021/01/parasite200128/parasite200128.html>. Acesso em: 10 jun. 2021. 1776-1042 |
url |
http://www.repositorio.ufop.br/jspui/handle/123456789/13834 https://doi.org/10.1051/parasite/2021036 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFOP instname:Universidade Federal de Ouro Preto (UFOP) instacron:UFOP |
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Universidade Federal de Ouro Preto (UFOP) |
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UFOP |
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UFOP |
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Repositório Institucional da UFOP |
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Repositório Institucional da UFOP |
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Repositório Institucional da UFOP - Universidade Federal de Ouro Preto (UFOP) |
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repositorio@ufop.edu.br |
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1813002850389721088 |