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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. © C.S. Freitas et al., published by EDP Sciences, 2021.


Camila S Freitas, Daniela P Lage, João A Oliveira-da-Silva, Rafaella R Costa, Débora V C Mendonça, Vívian T Martins, Thiago A R Reis, Luciana M R Antinarelli, Amanda S Machado, Grasiele S V Tavares, Fernanda F Ramos, Rory C F Brito, Fernanda Ludolf, Miguel A Chávez-Fumagalli, Bruno M Roatt, Gabriela S Ramos, Jennifer Munkert, Flaviano M Ottoni, Priscilla R V Campana, Mariana C Duarte, Denise U Gonçalves, Elaine S Coimbra, Fernão C Braga, Rodrigo M Pádua, Eduardo A F Coelho. In vitro and in vivo antileishmanial activity of β-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis. Parasite (Paris, France). 2021;28:38

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PMID: 33851916

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