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Physalins B and F, seco-steroids isolated from Physalis angulata L., strongly inhibit proliferation, ultrastructure and infectivity of Trypanosoma cruzi

Published online by Cambridge University Press:  04 September 2013

CÁSSIO S. MEIRA ,
ELISALVA T. GUIMARÃES ,
TANIRA M. BASTOS ,
DIOGO R. M. MOREIRA ,
THEREZINHA C. B. TOMASSINI ,
IVONE M. RIBEIRO ,
RICARDO R. DOS SANTOS  and
MILENA B. P. SOARES
CÁSSIO S. MEIRA
Affiliation:
Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz, Rua Waldemar Falcão, 121, Candeal, Salvador, Bahia, CEP: 40296-710, Brazil
ELISALVA T. GUIMARÃES
Affiliation:
Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz, Rua Waldemar Falcão, 121, Candeal, Salvador, Bahia, CEP: 40296-710, Brazil Departamento de Ciências da Vida, Universidade do Estado da Bahia, Rua Silveira Martins, 2555, Cabula, Salvador, Bahia, CEP: 41150-000, Brazil
TANIRA M. BASTOS
Affiliation:
Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz, Rua Waldemar Falcão, 121, Candeal, Salvador, Bahia, CEP: 40296-710, Brazil
DIOGO R. M. MOREIRA
Affiliation:
Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz, Rua Waldemar Falcão, 121, Candeal, Salvador, Bahia, CEP: 40296-710, Brazil
THEREZINHA C. B. TOMASSINI
Affiliation:
Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos (Farmanguinhos), Avenida Comandante Guaranys, Jacarepaguá, Rio de Janeiro, RJ, CEP: 22775-903, Brazil
IVONE M. RIBEIRO
Affiliation:
Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos (Farmanguinhos), Avenida Comandante Guaranys, Jacarepaguá, Rio de Janeiro, RJ, CEP: 22775-903, Brazil
RICARDO R. DOS SANTOS
Affiliation:
Hospital São Rafael, Centro de Biotecnologia e Terapia Celular, Avenida São Rafael, São Marcos, Salvador, Bahia, CEP: 41253-190, Brazil
MILENA B. P. SOARES*
Affiliation:
Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz, Rua Waldemar Falcão, 121, Candeal, Salvador, Bahia, CEP: 40296-710, Brazil Hospital São Rafael, Centro de Biotecnologia e Terapia Celular, Avenida São Rafael, São Marcos, Salvador, Bahia, CEP: 41253-190, Brazil
*
*Corresponding author. Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz. Rua Waldemar Falcão, 121, Candeal, Salvador, Bahia, 40296-710, Brazil. E-mail: [email protected]
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Summary

We previously observed that physalins have immunomodulatory properties, as well as antileishmanial and antiplasmodial activities. Here, we investigated the anti-Trypanosoma cruzi activity of physalins B, D, F and G. We found that physalins B and F were the most potent compounds against trypomastigote and epimastigote forms of T. cruzi. Electron microscopy of trypomastigotes incubated with physalin B showed disruption of kinetoplast, alterations in Golgi apparatus and endoplasmic reticulum, followed by the formation of myelin-like figures, which were stained with MDC to confirm their autophagic vacuole identity. Physalin B-mediated alteration in Golgi apparatus was likely due to T. cruzi protease perturbation; however physalins did not inhibit activity of the trypanosomal protease cruzain. Flow cytometry examination showed that cell death is mainly caused by necrosis. Treatment with physalins reduced the invasion process, as well as intracellular parasite development in macrophage cell culture, with a potency similar to benznidazole. We observed that a combination of physalins and benznidazole has a greater anti-T. cruzi activity than when compounds were used alone. These results indicate that physalins, specifically B and F, are potent and selective trypanocidal agents. They cause structural alterations and induce autophagy, which ultimately lead to parasite cell death by a necrotic process.

Keywords

Chagas diseaseTrypanosoma cruziautophagyseco-steroidsphysalins
Type
Research Article
Information
Parasitology , Volume 140 , Issue 14 , December 2013 , pp. 1811 - 1821
Copyright
Copyright © Cambridge University Press 2013 

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