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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Ergosterol isolated from the basidiomycete Pleurotus salmoneostramineus affects Trypanosoma cruzi plasma membrane and mitochondria

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Autor(es):
Alexandre, Tatiana Rodrigues ; Lima, Marta Lopes ; Galuppo, Mariana Kolos ; Mesquita, Juliana Tonini ; do Nascimento, Matilia Ana ; dos Santos, Augusto Leonardo ; Sartorelli, Patricia ; Pimenta, Daniel Carvalho ; Tempone, Andre Gustavo
Número total de Autores: 9
Tipo de documento: Artigo Científico
Fonte: Journal of Venomous Animals and Toxins including Tropical Diseases; v. 23, n. 1 MAY 30 2017.
Citações Web of Science: 4
Resumo

Background: Major drawbacks of the available treatment against Chagas disease (American trypanosomiasis) include its toxicity and therapeutic inefficiency in the chronic phase of the infection, which makes it a concern among neglected diseases. Therefore, the discovery of alternative drugs for treating chronic Chagas disease requires immediate action. In this work, we evaluated the mushroom Pleurotus salmoneostramineus in the search for potential antiparasitic compounds. Methods: Fruit bodies of the basidiomycete Pleurotus salmoneostramineus were triturated and submitted to organic solvent extraction. After liquid-liquid partition of the crude extract, three fractions were obtained and the bioguided fractionation study was conducted to isolate the active metabolites. The elucidation of the chemical structure was performed using GC-MS and NMR techniques. The biological assays for antiparasitic activity were carried out using trypomastigotes of Trypanosoma cruzi and murine macrophages for mammalian cytotoxicity. The mechanism of action of the isolated compound used different fluorescent probes to evaluate the plasma membrane permeability, the potential of the mitochondrial membrane and the intracellular levels of reactive oxygen species (ROS). Results: The most abundant fraction showing the antiparasitic activity was isolated and chemically elucidated, confirming the presence of ergosterol. It showed anti-Trypanosoma cruzi activity against trypomastigotes, with an IC50 value of 51.3 mu g/mL. The compound demonstrated no cytotoxicity against mammalian cells to the maximal tested concentration of 200 mu g/mL. The mechanism of action of ergosterol in Trypanosoma cruzi trypomastigotes resulted in permeabilization of the plasma membrane, as well as depolarization of mitochondrial membrane potential, leading to parasite death. Nevertheless, no increase in ROS levels could be observed, suggesting damages to plasma membrane rather than an induction of oxidative stress in the parasite. Conclusions: The selection of naturally antiparasitic secondary metabolites in basidiomycetes, such as ergosterol, may provide potential scaffolds for drug design studies against neglected diseases. (AU)

Processo FAPESP: 13/50228-8 - Componentes da biodiversidade, e seus caracteres metabólicos, de ilhas do Brasil - uma abordagem integrada
Beneficiário:Roberto Gomes de Souza Berlinck
Linha de fomento: Auxílio à Pesquisa - Programa BIOTA - Temático
Processo FAPESP: 16/24985-4 - Estudo da composição química de fungos e plantas da Mata Atlântica visando o potencial antitumoral, antiparasitário e antimicrobiano
Beneficiário:Patricia Sartorelli
Linha de fomento: Auxílio à Pesquisa - Regular