In vitro and in vivo antiparasitic activity of Physalis angulata L. concentrated ethanolic extract against Trypanosoma cruzi.
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.
['Meira|Cássio Santana|CS|', 'Guimarães|Elisalva Teixeira|ET|', 'Dos Santos|Jamyle Andrade Ferreira|JA|', 'Moreira|Diogo Rodrigo Magalhães|DR|', 'Nogueira|Renata Campos|RC|', 'Tomassini|Therezinha Coelho Barbosa|TC|', 'Ribeiro|Ivone Maria|IM|', 'de Souza|Claudia Valeria Campos|CV|', 'Ribeiro Dos Santos|Ricardo|R|', 'Soares|Milena Botelho Pereira|MB|']
D000818:Animals D014355:Chagas Disease D005260:Female D017737:Macrophages, Peritoneal D051379:Mice D008807:Mice, Inbred BALB C D018512:Parasitemia D032321:Physalis D010936:Plant Extracts D014344:Trypanocidal Agents D014349:Trypanosoma cruzi
Physalis angulata Trypanosoma cruzi Chagas disease Drug combination Plant extract