title: In vitro and in vivo antiparasitic activity of Physalis angulata L. concentrated ethanolic extract against Trypanosoma cruzi.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.
authors.forename: Cássio Santana
authors.initials: CS
authors.lastname: Meira
authors.affiliation: Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil; Universidade do Estado da Bahia, Salvador, Bahia, Brazil.
authors.forename: Elisalva Teixeira
authors.initials: ET
authors.lastname: Guimarães
authors.affiliation: Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil; Universidade do Estado da Bahia, Salvador, Bahia, Brazil.
authors.forename: Jamyle Andrade Ferreira
authors.initials: JA
authors.lastname: Dos Santos
authors.affiliation: Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.
authors.forename: Diogo Rodrigo Magalhães
authors.initials: DR
authors.lastname: Moreira
authors.affiliation: Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.
authors.forename: Renata Campos
authors.initials: RC
authors.lastname: Nogueira
authors.affiliation: Laboratório de Química de Produtos Naturais-PN2-Extração, Isolamento e Purificação, Farmanguinhos-Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Therezinha Coelho Barbosa
authors.initials: TC
authors.lastname: Tomassini
authors.affiliation: Laboratório de Química de Produtos Naturais-PN2-Extração, Isolamento e Purificação, Farmanguinhos-Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Ivone Maria
authors.initials: IM
authors.lastname: Ribeiro
authors.affiliation: Laboratório de Química de Produtos Naturais-PN2-Extração, Isolamento e Purificação, Farmanguinhos-Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Claudia Valeria Campos
authors.initials: CV
authors.lastname: de Souza
authors.affiliation: Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, Salvador, BA, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ribeiro Dos Santos
authors.affiliation: Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil; Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, Salvador, BA, Brazil. Electronic address: milenabpsoares@gmail.com.
authors.forename: Milena Botelho Pereira
authors.initials: MB
authors.lastname: Soares
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy; D005260:Female; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D018512:Parasitemia / Q000188:drug therapy; D032321:Physalis / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D010936:Plant Extracts; D014344:Trypanocidal Agents
keywords: Chagas disease; Drug combination; Physalis angulata; Plant extract; Trypanosoma cruzi