Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/7878
Title: Physalins B and F, seco-steroids isolated from Physalis angulata L., strongly inhibit proliferation, ultrastructure and infectivity of Trypanosoma cruzi.
Authors: Meira, Cássio Santana
Guimarães, Elisalva Teixeira
Bastos, Tanira Matutino
Moreira, Diogo Rodrigo Magalhães
Tomassini, Therezinha Coelho Barbosa
Ribeiro, Ivone Maria
Santos, Ricardo Ribeiro dos
Soares, Milena Botelho Pereira
Affilliation: Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade do Estado da Bahia. Departamento de Ciências da Vida. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos (Farmanguinhos). Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos (Farmanguinhos). Rio de Janeiro, RJ, Brasil
Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil
Abstract: 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 disease
Trypanosoma cruzi
Autophagy
Seco-steroids
Physalins
Issue Date: 2013
Publisher: Cambridge University Press
Citation: MEIRA, C. S. et al. and infectivity of Trypanosoma cruzi. Parasitology, v. 140, n. 14, p. 1811-1821, 2013.
DOI: 10.1017/S0031182013001297
ISSN: 1469-8161
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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