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JAC Advance Access published online on May 19, 2009
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkp170
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Activity of physalins purified from Physalis angulata in in vitro and in vivo models of cutaneous leishmaniasis

Elisalva T. Guimarães1, Milena S. Lima1, Luana A. Santos1, Ivone M. Ribeiro2, Therezinha B. C. Tomassini2, Ricardo Ribeiro dos Santos1,3, Washington L. C. dos Santos1 and Milena B. P. Soares1,3,*

1 Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brazil 2 FarManguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil 3 Hospital São Rafael, Salvador, BA, Brazil

Received 29 January 2009; returned 8 March 2009; revised 8 April 2009; accepted 16 April 2009

* Corresponding author. Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão, 121 Candeal, Salvador, BA 40296-710, Brazil. Tel: +55-71-3176-2260; Fax: +55-71-3176-2272; E-mail: milenabpsoares{at}gmail.com

Objectives: We have previously demonstrated the immunomodulatory effects of physalins, secosteroids purified from Physalis angulata. Here we investigate the antileishmanial activity of physalins in vitro and in vivo in a model of cutaneous leishmaniasis.

Methods: The antileishmanial activity of physalins B, D and F was tested in Leishmania-infected macrophage cultures. For the in vivo studies, BALB/c mice were infected with Leishmania amazonensis subcutaneously in the ear pinna and treated with physalin F by topical administration.

Results: Physalins B and F were able to reduce the percentage of Leishmania-infected macrophages and the intracellular parasite number in vitro at concentrations non-cytotoxic to macrophages. More importantly, topical treatment with physalin F significantly reduced the lesion size, the parasite load and histopathological alterations in BALB/c mice infected with L. amazonensis.

Conclusions: Our results demonstrate the potent antileishmanial activity of physalins, especially physalin F, and suggest these molecules as the basis for the development of new therapeutic options for cutaneous leishmaniasis.

Key Words: infections , macrophages , mice , secosteroids , therapy


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