Abstract | BACKGROUND: The current treatment of Chagas disease, endemic in Latin America and emerging in several countries, is limited by the frequent side effects and variable efficacy of benznidazole. Natural products are an important source for the search for new drugs. AIM/HYPOTHESIS: Considering the great potential of natural products as antiparasitic agents, we investigated the anti-Trypanosoma cruzi activity of a concentrated ethanolic extract of Physalis angulata (EEPA). METHODS: Cytotoxicity to mammalian cells was determined using mouse peritoneal macrophages. The antiparasitic activity was evaluated against axenic epimastigote and bloodstream trypomastigote forms of T. cruzi, and against amastigote forms using T. cruzi-infected macrophages. Cell death mechanism was determined in trypomastigotes by flow cytometry analysis after annexin V and propidium iodide staining. The efficacy of EEPA was examined in vivo in an acute model of infection by monitoring blood parasitaemia and survival rate 30 days after treatment. The effect against trypomastigotes of EEPA and benznidazole acting in combination was evaluated. RESULTS: EEPA effectively inhibits the epimastigote growth (IC50 2.9 ± 0.1 µM) and reduces bloodstream trypomastigote viability (EC50 1.7 ± 0.5 µM). It causes parasite cell death by necrosis. EEPA impairs parasite infectivity as well as amastigote development in concentrations noncytotoxic to mammalian cells. In mice acutely-infected with T. cruzi, EEPA reduced the blood parasitaemia in 72.7%. When combined with benznidazole, EEPA showed a synergistic anti-T. cruzi activity, displaying CI values of 0.8 ± 0.07 at EC50 and 0.83 ± 0.1 at EC90. CONCLUSION: EEPA has antiparasitic activity against T. cruzi, causing cell death by necrosis and showing synergistic activity with benznidazole. These findings were reinforced by the observed efficacy of EEPA in reducing parasite load in T. cruzi-mice. Therefore, this represents an important source of antiparasitic natural products.
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Authors | Cássio Santana Meira, Elisalva Teixeira Guimarães, Jamyle Andrade Ferreira Dos Santos, Diogo Rodrigo Magalhães Moreira, Renata Campos Nogueira, Therezinha Coelho Barbosa Tomassini, Ivone Maria Ribeiro, Claudia Valeria Campos de Souza, Ricardo Ribeiro Dos Santos, Milena Botelho Pereira Soares |
Journal | Phytomedicine : international journal of phytotherapy and phytopharmacology
(Phytomedicine)
Vol. 22
Issue 11
Pg. 969-74
(Oct 15 2015)
ISSN: 1618-095X [Electronic] Germany |
PMID | 26407938
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier GmbH. All rights reserved. |
Chemical References |
- Plant Extracts
- Trypanocidal Agents
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Topics |
- Animals
- Chagas Disease
(drug therapy)
- Female
- Macrophages, Peritoneal
(drug effects)
- Mice
- Mice, Inbred BALB C
- Parasitemia
(drug therapy)
- Physalis
(chemistry)
- Plant Extracts
(pharmacology)
- Trypanocidal Agents
(pharmacology)
- Trypanosoma cruzi
(drug effects)
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