Ergosterol isolated from the basidiomycete Pleurotus salmoneostramineus affects Trypanosoma cruzi plasma membrane and mitochondria
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | The Journal of venomous animals and toxins including tropical diseases (Online) |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992017000100313 |
Resumo: | Abstract 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 μg/mL. The compound demonstrated no cytotoxicity against mammalian cells to the maximal tested concentration of 200 μg/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. |
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The Journal of venomous animals and toxins including tropical diseases (Online) |
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Ergosterol isolated from the basidiomycete Pleurotus salmoneostramineus affects Trypanosoma cruzi plasma membrane and mitochondriaPleurotus salmoneostramineusErgosterolTrypanosoma cruziMechanism of actionAbstract 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 μg/mL. The compound demonstrated no cytotoxicity against mammalian cells to the maximal tested concentration of 200 μg/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.Centro de Estudos de Venenos e Animais Peçonhentos (CEVAP/UNESP)2017-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992017000100313Journal of Venomous Animals and Toxins including Tropical Diseases v.23 2017reponame:The Journal of venomous animals and toxins including tropical diseases (Online)instname:Universidade Estadual Paulista (UNESP)instacron:UNESP10.1186/s40409-017-0120-0info:eu-repo/semantics/openAccessAlexandre,Tatiana RodriguesLima,Marta LopesGaluppo,Mariana KolosMesquita,Juliana ToniniNascimento,Matilia Ana doSantos,Augusto Leonardo dosSartorelli,PatriciaPimenta,Daniel CarvalhoTempone,Andre Gustavoeng2017-07-03T00:00:00Zoai:scielo:S1678-91992017000100313Revistahttp://www.scielo.br/jvatitdPUBhttps://old.scielo.br/oai/scielo-oai.php||editorial@jvat.org.br1678-91991678-9180opendoar:2017-07-03T00:00The Journal of venomous animals and toxins including tropical diseases (Online) - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Ergosterol isolated from the basidiomycete Pleurotus salmoneostramineus affects Trypanosoma cruzi plasma membrane and mitochondria |
title |
Ergosterol isolated from the basidiomycete Pleurotus salmoneostramineus affects Trypanosoma cruzi plasma membrane and mitochondria |
spellingShingle |
Ergosterol isolated from the basidiomycete Pleurotus salmoneostramineus affects Trypanosoma cruzi plasma membrane and mitochondria Alexandre,Tatiana Rodrigues Pleurotus salmoneostramineus Ergosterol Trypanosoma cruzi Mechanism of action |
title_short |
Ergosterol isolated from the basidiomycete Pleurotus salmoneostramineus affects Trypanosoma cruzi plasma membrane and mitochondria |
title_full |
Ergosterol isolated from the basidiomycete Pleurotus salmoneostramineus affects Trypanosoma cruzi plasma membrane and mitochondria |
title_fullStr |
Ergosterol isolated from the basidiomycete Pleurotus salmoneostramineus affects Trypanosoma cruzi plasma membrane and mitochondria |
title_full_unstemmed |
Ergosterol isolated from the basidiomycete Pleurotus salmoneostramineus affects Trypanosoma cruzi plasma membrane and mitochondria |
title_sort |
Ergosterol isolated from the basidiomycete Pleurotus salmoneostramineus affects Trypanosoma cruzi plasma membrane and mitochondria |
author |
Alexandre,Tatiana Rodrigues |
author_facet |
Alexandre,Tatiana Rodrigues Lima,Marta Lopes Galuppo,Mariana Kolos Mesquita,Juliana Tonini Nascimento,Matilia Ana do Santos,Augusto Leonardo dos Sartorelli,Patricia Pimenta,Daniel Carvalho Tempone,Andre Gustavo |
author_role |
author |
author2 |
Lima,Marta Lopes Galuppo,Mariana Kolos Mesquita,Juliana Tonini Nascimento,Matilia Ana do Santos,Augusto Leonardo dos Sartorelli,Patricia Pimenta,Daniel Carvalho Tempone,Andre Gustavo |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Alexandre,Tatiana Rodrigues Lima,Marta Lopes Galuppo,Mariana Kolos Mesquita,Juliana Tonini Nascimento,Matilia Ana do Santos,Augusto Leonardo dos Sartorelli,Patricia Pimenta,Daniel Carvalho Tempone,Andre Gustavo |
dc.subject.por.fl_str_mv |
Pleurotus salmoneostramineus Ergosterol Trypanosoma cruzi Mechanism of action |
topic |
Pleurotus salmoneostramineus Ergosterol Trypanosoma cruzi Mechanism of action |
description |
Abstract 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 μg/mL. The compound demonstrated no cytotoxicity against mammalian cells to the maximal tested concentration of 200 μg/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. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-01-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992017000100313 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992017000100313 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1186/s40409-017-0120-0 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Centro de Estudos de Venenos e Animais Peçonhentos (CEVAP/UNESP) |
publisher.none.fl_str_mv |
Centro de Estudos de Venenos e Animais Peçonhentos (CEVAP/UNESP) |
dc.source.none.fl_str_mv |
Journal of Venomous Animals and Toxins including Tropical Diseases v.23 2017 reponame:The Journal of venomous animals and toxins including tropical diseases (Online) instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
The Journal of venomous animals and toxins including tropical diseases (Online) |
collection |
The Journal of venomous animals and toxins including tropical diseases (Online) |
repository.name.fl_str_mv |
The Journal of venomous animals and toxins including tropical diseases (Online) - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
||editorial@jvat.org.br |
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1748958540139069440 |