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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/32036
Ver los metadatos del registro completo
id |
CONICETDig_6384a7d45814f26ff171d7652c8889e2 |
---|---|
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 |
_version_ |
1844614318673362944 |
score |
13.070432 |