Ergosterol isolated from the basidiomycete Pleurotus salmoneostramineus affects Trypanosoma cruzi plasma membrane and mitochondriaReportar como inadecuado




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Journal of Venomous Animals and Toxins including Tropical Diseases

, 23:30

Hyphenated mass spectrometry strategies as tools for unveiling peptide toxins with potential therapeutic application

Abstract

BackgroundMajor 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.

MethodsFruit 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.

ResultsThe 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.

ConclusionsThe selection of naturally antiparasitic secondary metabolites in basidiomycetes, such as ergosterol, may provide potential scaffolds for drug design studies against neglected diseases.

KeywordsPleurotus salmoneostramineus Ergosterol Trypanosoma cruzi Mechanism of action AbbreviationsACDAcute Chagas disease

CCColumn chromatography

CC5050% cytotoxic concentration

CDChagas disease

CPSColumn Pleurotus salmoneostramineus

DMSODimethyl sulfoxide

DNDiDrugs for Neglected Diseases Initiative

EtOAcEthyl acetate

FBSFetal bovine serum

HBSSHank’s Balanced Salt Solution

IC5050% inhibitory concentration

PBSPhosphate-buffered saline

ROSReactive oxygen species

RPMIRoswell Park Memorial Institute Medium

SBPSterol biosynthetic pathway

SDSSodium dodecyl sulfate

TcCPY51T. cruzi CPY51

TLCThin layer chromatography

Electronic supplementary materialThe online version of this article doi:10.1186-s40409-017-0120-0 contains supplementary material, which is available to authorized users.





Autor: Tatiana Rodrigues Alexandre - Marta Lopes Lima - Mariana Kolos Galuppo - Juliana Tonini Mesquita - Matilia Ana do Nascim

Fuente: https://link.springer.com/







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