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

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art_ALEXANDRE_Ergosterol_isolated_from_the_basidiomycete_Pleurotus_salmoneostramineus_affects_2017.PDF (587.33 KB)
Citações na Scopus
26
Tipo de produção
article
Data de publicação
2017
DOI
SciELO
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
BIOMED CENTRAL LTD
Autores
ALEXANDRE, Tatiana Rodrigues
GALUPPO, Mariana Kolos
MESQUITA, Juliana Tonini
NASCIMENTO, Matilia Ana do
SANTOS, Augusto Leonardo dos
SARTORELLI, Patricia
PIMENTA, Daniel Carvalho
TEMPONE, Andre Gustavo
Citação
JOURNAL OF VENOMOUS ANIMALS AND TOXINS INCLUDING TROPICAL DISEASES, v.23, n.1, article ID 30, 10p, 2017
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
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.
Palavras-chave
Pleurotus salmoneostramineus, Ergosterol, Trypanosoma cruzi, Mechanism of action
URI
https://observatorio.fm.usp.br/handle/OPI/21614
Referências
  1. Barrero AF, 1998, J NAT PROD, V61, P1491, DOI 10.1021/np980199h
  2. Bestetti RB, 2011, INT J CARDIOL, V147, P172, DOI 10.1016/j.ijcard.2010.12.020
  3. Bettiol E, 2009, PLOS NEGLECT TROP D, V3, DOI 10.1371/journal.pntd.0000384
  4. Borges GM, 2013, BRAZ J MICROBIOL, V44, P1059, DOI 10.1590/S1517-83822014005000019
  5. Boscardin SB, 2010, J CELL MOL MED, V14, P1373, DOI 10.1111/j.1582-4934.2010.01007.x
  6. Braga MV, 2004, INT J ANTIMICROB AG, V24, P72, DOI 10.1016/j.ijantimicag.2003.12.009
  7. Brilhante RSN, 2015, J APPL MICROBIOL, V119, P962, DOI 10.1111/jam.12891
  8. Chatelain E, 2015, DRUG DES DEV THER, V9, P4807, DOI 10.2147/DDDT.S90208
  9. Chowdhury MMH, 2015, ANN CLIN MICROB ANTI, V14, DOI 10.1186/s12941-015-0067-3
  10. Croft SL, 2005, TRENDS PARASITOL, V21, P508, DOI 10.1016/j.pt.2005.08.026
  11. De Souze W, 2014, FRONT IMMUNOL, V5, DOI 10.3389/fimmu.2014.00339
  12. DECASTRO SL, 1993, BRAZ J MED BIOL RES, V26, P1219
  13. de Goes CE, 2017, INT J CARDIOL, V235, P176
  14. de Soeiro MN, 2013, ANTIMICROB AGENTS CH, V57, P4151
  15. Duschak Vilma G, 2007, Recent Pat Antiinfect Drug Discov, V2, P19, DOI 10.2174/157489107779561625
  16. Elsayed E. A., 2014, MEDIAT INFLAMM, V2014
  17. Francisco AF, 2015, ANTIMICROB AGENTS CH, V59, P4653, DOI 10.1128/AAC.00520-15
  18. GALLI G, 1967, STEROIDS, V10, P189, DOI 10.1016/0039-128X(67)90046-3
  19. Ginger ML, 2000, EUR J BIOCHEM, V267, P2555, DOI 10.1046/j.1432-1327.2000.01261.x
  20. Lai TK, 2012, CHEM BIODIVERS, V9, P1517, DOI 10.1002/cbdv.201100272
  21. LAZARDI K, 1990, ANTIMICROB AGENTS CH, V34, P2097
  22. Lazarin-Bidoia D, 2013, FREE RADICAL BIO MED, V60, P17, DOI 10.1016/j.freeradbiomed.2013.01.008
  23. Lo YC, 2012, INT J MED MUSHROOMS, V14, P357
  24. Pereira PCM, 2013, J VENOM ANIM TOXINS, V19, DOI 10.1186/1678-9199-19-34
  25. Mathur R, 2015, FASEB J, V29, P4201, DOI 10.1096/fj.15-272757
  26. Mercer AE, 2007, J BIOL CHEM, V282, P9372, DOI 10.1074/jbc.M610375200
  27. Meshnick SR, 2002, INT J PARASITOL, V32, P1655, DOI 10.1016/S0020-7519(02)00194-7
  28. Mikus Judith, 2000, Parasitology International, V48, P265, DOI 10.1016/S1383-5769(99)00020-3
  29. Moraes CB, 2014, SCI REP-UK, V4, DOI 10.1038/srep04703
  30. Nganso Yves Oscar D, 2011, Sci Pharm, V79, P137, DOI 10.3797/scipharm.1012-10
  31. Pinto EG, 2014, J VENOM ANIM TOXINS, V20, DOI 10.1186/1678-9199-20-50
  32. Planer JD, 2014, PLOS NEGLECT TROP D, V8, DOI 10.1371/journal.pntd.0002977
  33. Quinones W, 2004, EXP PARASITOL, V106, P135, DOI 10.1016/j.exppara.2004.03.006
  34. Ramirez-Macias I, 2012, AM J TROP MED HYG, V87, P481, DOI 10.4269/ajtmh.2012.11-0471
  35. Ramos-Ligonio A, 2012, PHYTOTHER RES, V26, P938, DOI 10.1002/ptr.3653
  36. Rea A, 2013, PLOS NEGLECT TROP D, V7, DOI 10.1371/journal.pntd.0002556
  37. Roberts CW, 2003, MOL BIOCHEM PARASIT, V126, P129, DOI 10.1016/S0166-6851(02)00280-3
  38. Rodrigues CO, 2001, J EUKARYOT MICROBIOL, V48, P588, DOI 10.1111/j.1550-7408.2001.tb00195.x
  39. Romanha AJ, 2010, MEM I OSWALDO CRUZ, V105, P233, DOI 10.1590/S0074-02762010000200022
  40. Rosa LH, 2009, ANTON LEEUW INT J G, V95, P227, DOI 10.1007/s10482-009-9306-y
  41. Menna-Barreto RFS, 2014, BIOMED RES INT, DOI 10.1155/2014/614014
  42. Santos MFC, 2015, J NAT PROD, V78, P1101, DOI 10.1021/acs.jnatprod.5b00070
  43. Simoes-Silva MR, 2016, ANTIMICROB AGENTS CH, V60, P4701, DOI 10.1128/AAC.01788-15
  44. Souza-Fagundes EM, 2010, BRAZ J MED BIOL RES, V43, P1054, DOI [10.1590/S0100-879X2010007500108, 10.1590/S0100-879X2010001100007]
  45. Tempone AG, 2008, TOXICON, V52, P13, DOI 10.1016/j.toxicon.2008.05.008
  46. URBINA JA, 1991, ANTIMICROB AGENTS CH, V35, P730
  47. Usami A, 2014, J OLEO SCI, V63, P1323, DOI 10.5650/jos.ess14147
  48. Verma S, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0025273
  49. Viegelmann C, 2014, MAR DRUGS, V12, P2937, DOI 10.3390/md12052937
  50. WHO, CHAG DIS
  51. WRIGHT JLC, 1979, CAN J CHEM, V57, P2569, DOI 10.1139/v79-415
  52. Wu XL, 2010, J GEN APPL MICROBIOL, V56, P231
  53. Yang TS, 2013, BBA-BIOMEMBRANES, V1828, P1794, DOI 10.1016/j.bbamem.2013.03.021
  54. Yoon KN, 2012, INT J MED MUSHROOMS, V14, P27

Coleções
Artigos e Materiais de Revistas Científicas - IMT