We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
In vitro and in vivo antileishmanial activity of β-acetyl-digitoxin, a cardenolide of Digitalis lanata potentially useful to treat visceral leishmaniasis.
- Authors
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.
- Abstract
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.
- Subjects
CARDENOLIDES; DRUG resistance in bacteria; LEISHMANIA infantum; MACROPHAGES; DRUG side effects
- Publication
Parasite (1252607X), 2021, Vol 28, p1
- ISSN
1252-607X
- Publication type
Article
- DOI
10.1051/parasite/2021036