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In vitro and in vivo antileishmanial activity of β-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis

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 β-acetyl-digitoxin (b-AD), a ca...

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Autores principales: Freitas, Camila S., Lage, Daniela P., Oliveira-da-Silva, João A., Costa, Rafaella R., Mendonça, Débora V.C., Martins, Vívian T., Reis, Thiago A.R., Antinarelli, Luciana M.R., Machado, Amanda S., Tavares, Grasiele S.V., Ramos, Fernanda F., Brito, Rory C.F., Ludolf, Fernanda, Chávez-Fumagalli, Miguel A., Roatt, Bruno M., Ramos, Gabriela S., Munkert, Jennifer, Ottoni, Flaviano M., Campana, Priscilla R.V., Duarte, Mariana C., Gonçalves, Denise U., Coimbra, Elaine S., Braga, Fernão C., Pádua, Rodrigo M., Coelho, Eduardo A.F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: EDP Sciences 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045677/
https://www.ncbi.nlm.nih.gov/pubmed/33851916
http://dx.doi.org/10.1051/parasite/2021036
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author Freitas, Camila S.
Lage, Daniela P.
Oliveira-da-Silva, João A.
Costa, Rafaella R.
Mendonça, Débora V.C.
Martins, Vívian T.
Reis, Thiago A.R.
Antinarelli, Luciana M.R.
Machado, Amanda S.
Tavares, Grasiele S.V.
Ramos, Fernanda F.
Brito, Rory C.F.
Ludolf, Fernanda
Chávez-Fumagalli, Miguel A.
Roatt, Bruno M.
Ramos, Gabriela S.
Munkert, Jennifer
Ottoni, Flaviano M.
Campana, Priscilla R.V.
Duarte, Mariana C.
Gonçalves, Denise U.
Coimbra, Elaine S.
Braga, Fernão C.
Pádua, Rodrigo M.
Coelho, Eduardo A.F.
author_facet Freitas, Camila S.
Lage, Daniela P.
Oliveira-da-Silva, João A.
Costa, Rafaella R.
Mendonça, Débora V.C.
Martins, Vívian T.
Reis, Thiago A.R.
Antinarelli, Luciana M.R.
Machado, Amanda S.
Tavares, Grasiele S.V.
Ramos, Fernanda F.
Brito, Rory C.F.
Ludolf, Fernanda
Chávez-Fumagalli, Miguel A.
Roatt, Bruno M.
Ramos, Gabriela S.
Munkert, Jennifer
Ottoni, Flaviano M.
Campana, Priscilla R.V.
Duarte, Mariana C.
Gonçalves, Denise U.
Coimbra, Elaine S.
Braga, Fernão C.
Pádua, Rodrigo M.
Coelho, Eduardo A.F.
author_sort Freitas, Camila S.
collection PubMed
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 β-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-γ, IL-12, TNF-α, GM-CSF, nitrite and specific IgG2a antibodies, in addition to low IL-4 and IL-10 contents, along with higher IFN-γ-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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spelling pubmed-80456772021-04-21 In vitro and in vivo antileishmanial activity of β-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis Freitas, Camila S. Lage, Daniela P. Oliveira-da-Silva, João A. Costa, Rafaella R. Mendonça, Débora V.C. Martins, Vívian T. Reis, Thiago A.R. Antinarelli, Luciana M.R. Machado, Amanda S. Tavares, Grasiele S.V. Ramos, Fernanda F. Brito, Rory C.F. Ludolf, Fernanda Chávez-Fumagalli, Miguel A. Roatt, Bruno M. Ramos, Gabriela S. Munkert, Jennifer Ottoni, Flaviano M. Campana, Priscilla R.V. Duarte, Mariana C. Gonçalves, Denise U. Coimbra, Elaine S. Braga, Fernão C. Pádua, Rodrigo M. Coelho, Eduardo A.F. Parasite Research Article 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 β-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-γ, IL-12, TNF-α, GM-CSF, nitrite and specific IgG2a antibodies, in addition to low IL-4 and IL-10 contents, along with higher IFN-γ-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. EDP Sciences 2021-04-14 /pmc/articles/PMC8045677/ /pubmed/33851916 http://dx.doi.org/10.1051/parasite/2021036 Text en © C.S. Freitas et al., published by EDP Sciences, 2021 https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Freitas, Camila S.
Lage, Daniela P.
Oliveira-da-Silva, João A.
Costa, Rafaella R.
Mendonça, Débora V.C.
Martins, Vívian T.
Reis, Thiago A.R.
Antinarelli, Luciana M.R.
Machado, Amanda S.
Tavares, Grasiele S.V.
Ramos, Fernanda F.
Brito, Rory C.F.
Ludolf, Fernanda
Chávez-Fumagalli, Miguel A.
Roatt, Bruno M.
Ramos, Gabriela S.
Munkert, Jennifer
Ottoni, Flaviano M.
Campana, Priscilla R.V.
Duarte, Mariana C.
Gonçalves, Denise U.
Coimbra, Elaine S.
Braga, Fernão C.
Pádua, Rodrigo M.
Coelho, Eduardo A.F.
In vitro and in vivo antileishmanial activity of β-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis
title In vitro and in vivo antileishmanial activity of β-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis
title_full In vitro and in vivo antileishmanial activity of β-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis
title_fullStr In vitro and in vivo antileishmanial activity of β-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis
title_full_unstemmed In vitro and in vivo antileishmanial activity of β-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis
title_short In vitro and in vivo antileishmanial activity of β-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis
title_sort in vitro and in vivo antileishmanial activity of β-acetyl-digitoxin, a cardenolide of digitalis lanata potentially useful to treat visceral leishmaniasis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045677/
https://www.ncbi.nlm.nih.gov/pubmed/33851916
http://dx.doi.org/10.1051/parasite/2021036
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