Natural sesquiterpene lactones induce programmed cell death in Trypanosoma cruzi: a new therapeutic target?

Autores
Jimenez, V.; Kemmerling, U.; Paredes, Rogelio Claudio; Maya, J. D.; Sosa Escudero, Miguel Angel; Galanti, N.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BACKGROUND: Chagas disease or American Trypanosomiasis is caused by the flagellated protozoan parasite Trypanosoma cruzi (T. cruzi) and is recognized by the WHO as one of the world's 17 neglected tropical diseases. Only two drugs (Benznidazol, Bz and Nifurtimox, Nx) are currently accepted for treatment, however they cause severe adverse effects and their efficacy is still controversial. It is then important to explore for new drugs. PURPOSE: Programmed cell death (PCD) in parasites offers interesting new therapeutic targets. The aim of this work was to evaluate the induction of PCD in T. cruzi by two natural sesquiterpene lactones (STLs), dehydroleucodine (DhL) and helenalin (Hln) as compared with the two conventional drugs, Bz and Nx. MATERIAL AND METHODS: Hln and DhL were isolated from aerial parts of Gaillardia megapotamica and Artemisia douglassiana Besser, respectively. Purity of compounds (greater than 95%) was confirmed by (13)C-nuclear magnetic resonance, melting point analysis, and optical rotation. Induction of PCD in T. cruzi epimastigotes and trypomastigotes by DhL, Hln, Bz and Nx was assayed by phosphatidylserine exposure at the parasite surface and by detection of DNA fragmentation using the TUNEL assay. Trypanocidal activity of natural and synthetic compounds was assayed by measuring parasite viability using the MTT method. RESULTS: The two natural STLs, DhL and Hln, induce programmed cell death in both, the replicative epimastigote form and the infective trypomastigote form of T. cruzi. Interestingly, the two conventional antichagasic drugs (Bz and Nx) do not induce programmed cell death. A combination of DhL and either Bz or Nx showed an increased effect of natural compounds and synthetic drugs on the decrease of parasite viability. CONCLUSION: DhL and Hln induce programmed cell death in T. cruzi replicative epimastigote and infective trypomastigote forms, which is a different mechanism of action than the conventional drugs to kill the parasite. Therefore DhL and Hln may offer an interesting option for the treatment of Chagas disease, alone or in combination with conventional drugs.
Fil: Jimenez, V.. Universidad de Chile; Chile
Fil: Kemmerling, U.. Universidad de Chile; Chile
Fil: Paredes, Rogelio Claudio. Universidad Andrés Bello; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina
Fil: Maya, J. D.. Universidad de Chile; Chile
Fil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Galanti, N.. Universidad de Chile; Chile
Materia
Sesquiterpene Lactones
Trypanosoma Cruzi
Chagas Disease
Programmed Cell Death
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/32036

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oai_identifier_str oai:ri.conicet.gov.ar:11336/32036
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Natural sesquiterpene lactones induce programmed cell death in Trypanosoma cruzi: a new therapeutic target?Jimenez, V.Kemmerling, U.Paredes, Rogelio ClaudioMaya, J. D.Sosa Escudero, Miguel AngelGalanti, N.Sesquiterpene LactonesTrypanosoma CruziChagas DiseaseProgrammed Cell Deathhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1BACKGROUND: Chagas disease or American Trypanosomiasis is caused by the flagellated protozoan parasite Trypanosoma cruzi (T. cruzi) and is recognized by the WHO as one of the world's 17 neglected tropical diseases. Only two drugs (Benznidazol, Bz and Nifurtimox, Nx) are currently accepted for treatment, however they cause severe adverse effects and their efficacy is still controversial. It is then important to explore for new drugs. PURPOSE: Programmed cell death (PCD) in parasites offers interesting new therapeutic targets. The aim of this work was to evaluate the induction of PCD in T. cruzi by two natural sesquiterpene lactones (STLs), dehydroleucodine (DhL) and helenalin (Hln) as compared with the two conventional drugs, Bz and Nx. MATERIAL AND METHODS: Hln and DhL were isolated from aerial parts of Gaillardia megapotamica and Artemisia douglassiana Besser, respectively. Purity of compounds (greater than 95%) was confirmed by (13)C-nuclear magnetic resonance, melting point analysis, and optical rotation. Induction of PCD in T. cruzi epimastigotes and trypomastigotes by DhL, Hln, Bz and Nx was assayed by phosphatidylserine exposure at the parasite surface and by detection of DNA fragmentation using the TUNEL assay. Trypanocidal activity of natural and synthetic compounds was assayed by measuring parasite viability using the MTT method. RESULTS: The two natural STLs, DhL and Hln, induce programmed cell death in both, the replicative epimastigote form and the infective trypomastigote form of T. cruzi. Interestingly, the two conventional antichagasic drugs (Bz and Nx) do not induce programmed cell death. A combination of DhL and either Bz or Nx showed an increased effect of natural compounds and synthetic drugs on the decrease of parasite viability. CONCLUSION: DhL and Hln induce programmed cell death in T. cruzi replicative epimastigote and infective trypomastigote forms, which is a different mechanism of action than the conventional drugs to kill the parasite. Therefore DhL and Hln may offer an interesting option for the treatment of Chagas disease, alone or in combination with conventional drugs.Fil: Jimenez, V.. Universidad de Chile; ChileFil: Kemmerling, U.. Universidad de Chile; ChileFil: Paredes, Rogelio Claudio. Universidad Andrés Bello; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; ArgentinaFil: Maya, J. D.. Universidad de Chile; ChileFil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Galanti, N.. Universidad de Chile; ChileElsevier Gmbh2014-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/32036Galanti, N.; Sosa Escudero, Miguel Angel; Maya, J. D.; Paredes, Rogelio Claudio; Kemmerling, U.; Jimenez, V.; et al.; Natural sesquiterpene lactones induce programmed cell death in Trypanosoma cruzi: a new therapeutic target?; Elsevier Gmbh; Phytomedicine; 21; 11; 7-2014; 1411-14180944-7113CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0944711314002542info:eu-repo/semantics/altIdentifier/doi/10.1016/j.phymed.2014.06.005info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:30:56Zoai:ri.conicet.gov.ar:11336/32036instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:30:56.549CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Natural sesquiterpene lactones induce programmed cell death in Trypanosoma cruzi: a new therapeutic target?
title Natural sesquiterpene lactones induce programmed cell death in Trypanosoma cruzi: a new therapeutic target?
spellingShingle Natural sesquiterpene lactones induce programmed cell death in Trypanosoma cruzi: a new therapeutic target?
Jimenez, V.
Sesquiterpene Lactones
Trypanosoma Cruzi
Chagas Disease
Programmed Cell Death
title_short Natural sesquiterpene lactones induce programmed cell death in Trypanosoma cruzi: a new therapeutic target?
title_full Natural sesquiterpene lactones induce programmed cell death in Trypanosoma cruzi: a new therapeutic target?
title_fullStr Natural sesquiterpene lactones induce programmed cell death in Trypanosoma cruzi: a new therapeutic target?
title_full_unstemmed Natural sesquiterpene lactones induce programmed cell death in Trypanosoma cruzi: a new therapeutic target?
title_sort Natural sesquiterpene lactones induce programmed cell death in Trypanosoma cruzi: a new therapeutic target?
dc.creator.none.fl_str_mv Jimenez, V.
Kemmerling, U.
Paredes, Rogelio Claudio
Maya, J. D.
Sosa Escudero, Miguel Angel
Galanti, N.
author Jimenez, V.
author_facet Jimenez, V.
Kemmerling, U.
Paredes, Rogelio Claudio
Maya, J. D.
Sosa Escudero, Miguel Angel
Galanti, N.
author_role author
author2 Kemmerling, U.
Paredes, Rogelio Claudio
Maya, J. D.
Sosa Escudero, Miguel Angel
Galanti, N.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Sesquiterpene Lactones
Trypanosoma Cruzi
Chagas Disease
Programmed Cell Death
topic Sesquiterpene Lactones
Trypanosoma Cruzi
Chagas Disease
Programmed Cell Death
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv BACKGROUND: Chagas disease or American Trypanosomiasis is caused by the flagellated protozoan parasite Trypanosoma cruzi (T. cruzi) and is recognized by the WHO as one of the world's 17 neglected tropical diseases. Only two drugs (Benznidazol, Bz and Nifurtimox, Nx) are currently accepted for treatment, however they cause severe adverse effects and their efficacy is still controversial. It is then important to explore for new drugs. PURPOSE: Programmed cell death (PCD) in parasites offers interesting new therapeutic targets. The aim of this work was to evaluate the induction of PCD in T. cruzi by two natural sesquiterpene lactones (STLs), dehydroleucodine (DhL) and helenalin (Hln) as compared with the two conventional drugs, Bz and Nx. MATERIAL AND METHODS: Hln and DhL were isolated from aerial parts of Gaillardia megapotamica and Artemisia douglassiana Besser, respectively. Purity of compounds (greater than 95%) was confirmed by (13)C-nuclear magnetic resonance, melting point analysis, and optical rotation. Induction of PCD in T. cruzi epimastigotes and trypomastigotes by DhL, Hln, Bz and Nx was assayed by phosphatidylserine exposure at the parasite surface and by detection of DNA fragmentation using the TUNEL assay. Trypanocidal activity of natural and synthetic compounds was assayed by measuring parasite viability using the MTT method. RESULTS: The two natural STLs, DhL and Hln, induce programmed cell death in both, the replicative epimastigote form and the infective trypomastigote form of T. cruzi. Interestingly, the two conventional antichagasic drugs (Bz and Nx) do not induce programmed cell death. A combination of DhL and either Bz or Nx showed an increased effect of natural compounds and synthetic drugs on the decrease of parasite viability. CONCLUSION: DhL and Hln induce programmed cell death in T. cruzi replicative epimastigote and infective trypomastigote forms, which is a different mechanism of action than the conventional drugs to kill the parasite. Therefore DhL and Hln may offer an interesting option for the treatment of Chagas disease, alone or in combination with conventional drugs.
Fil: Jimenez, V.. Universidad de Chile; Chile
Fil: Kemmerling, U.. Universidad de Chile; Chile
Fil: Paredes, Rogelio Claudio. Universidad Andrés Bello; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina
Fil: Maya, J. D.. Universidad de Chile; Chile
Fil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Galanti, N.. Universidad de Chile; Chile
description BACKGROUND: Chagas disease or American Trypanosomiasis is caused by the flagellated protozoan parasite Trypanosoma cruzi (T. cruzi) and is recognized by the WHO as one of the world's 17 neglected tropical diseases. Only two drugs (Benznidazol, Bz and Nifurtimox, Nx) are currently accepted for treatment, however they cause severe adverse effects and their efficacy is still controversial. It is then important to explore for new drugs. PURPOSE: Programmed cell death (PCD) in parasites offers interesting new therapeutic targets. The aim of this work was to evaluate the induction of PCD in T. cruzi by two natural sesquiterpene lactones (STLs), dehydroleucodine (DhL) and helenalin (Hln) as compared with the two conventional drugs, Bz and Nx. MATERIAL AND METHODS: Hln and DhL were isolated from aerial parts of Gaillardia megapotamica and Artemisia douglassiana Besser, respectively. Purity of compounds (greater than 95%) was confirmed by (13)C-nuclear magnetic resonance, melting point analysis, and optical rotation. Induction of PCD in T. cruzi epimastigotes and trypomastigotes by DhL, Hln, Bz and Nx was assayed by phosphatidylserine exposure at the parasite surface and by detection of DNA fragmentation using the TUNEL assay. Trypanocidal activity of natural and synthetic compounds was assayed by measuring parasite viability using the MTT method. RESULTS: The two natural STLs, DhL and Hln, induce programmed cell death in both, the replicative epimastigote form and the infective trypomastigote form of T. cruzi. Interestingly, the two conventional antichagasic drugs (Bz and Nx) do not induce programmed cell death. A combination of DhL and either Bz or Nx showed an increased effect of natural compounds and synthetic drugs on the decrease of parasite viability. CONCLUSION: DhL and Hln induce programmed cell death in T. cruzi replicative epimastigote and infective trypomastigote forms, which is a different mechanism of action than the conventional drugs to kill the parasite. Therefore DhL and Hln may offer an interesting option for the treatment of Chagas disease, alone or in combination with conventional drugs.
publishDate 2014
dc.date.none.fl_str_mv 2014-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/32036
Galanti, N.; Sosa Escudero, Miguel Angel; Maya, J. D.; Paredes, Rogelio Claudio; Kemmerling, U.; Jimenez, V.; et al.; Natural sesquiterpene lactones induce programmed cell death in Trypanosoma cruzi: a new therapeutic target?; Elsevier Gmbh; Phytomedicine; 21; 11; 7-2014; 1411-1418
0944-7113
CONICET Digital
CONICET
url http://hdl.handle.net/11336/32036
identifier_str_mv Galanti, N.; Sosa Escudero, Miguel Angel; Maya, J. D.; Paredes, Rogelio Claudio; Kemmerling, U.; Jimenez, V.; et al.; Natural sesquiterpene lactones induce programmed cell death in Trypanosoma cruzi: a new therapeutic target?; Elsevier Gmbh; Phytomedicine; 21; 11; 7-2014; 1411-1418
0944-7113
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0944711314002542
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.phymed.2014.06.005
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Gmbh
publisher.none.fl_str_mv Elsevier Gmbh
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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