Behavioral and molecular bases of the anthelmintic activity of essential oils explored in the nematode Caenorhabditis elegans

Autores
Hernando, Guillermina Silvana; Turani, Ornella; Bouzat, Cecilia Beatriz
Año de publicación
2021
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Control of helminth infections in both human and veterinary med icine currently relies mainly on chemotherapy, but acquisition of resistance is an increasing problem that leads to the urgent need of discovery of novel drugs. C. elegans has demonstrated to be a model system for the discovery of new anthelmintics and for char acterizing their mechanisms of action and resistance. Essential oils (EOs) are natural products produced by aromatic plants. We per form paralysis assays of wild-type and mutant C. elegans strain to identify EOs with potential anthelmintic activities, reveal the active components, their target sites, and mechanisms of action. We found that EOs belonging to different orders produce rapid paralysis of C. elegans with EC50 values between 0.02-2 % EOs. All EOs test ed also inhibited egg hatching, a property related to anthelmintic ability. Thus, EOs mediate both rapid and long-term anthelmintic effects. We examined anthelmintic properties of terpenoids and phenylpropenes and determined that all compounds tested produce both paralysis and egg-hatching inhibition. By testing mutant worms, we identified the muscle L-AChR and GABA receptors as EOs and trans-cinnamaldehyde (TC, phenylpropene) targets. Thus, by modulating two receptors with key roles in worm motility, these EOs emerge as novel sources of anthelmintic compounds. To unequivo cally confirm that these receptors are targets of TC and to describe the mechanism by which they affect these receptors, we performed whole-cell and single-channel recordings from C. elegans muscle cells. Electrophysiological recordings at the single-channel level re vealed that TC reduces L-AChR channel activity without affecting channel properties. The results are compatible with the action of these drugs as allosteric inhibitors. It is hoped that this work can update the recent progress on natural nematicide discoveries and provide new ideas for the design and mechanism of action studies of anthelmintics.
Fil: Hernando, Guillermina Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Turani, Ornella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
LXVI Reunión anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión anual de la Sociedad Argentina de Immunología; LIII Reunión anual de la Asociación Argentina de Farmacología Experimental y XI Reunión anual de la Asociación Argentina de Nanomedicinas
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Farmacología Experimental
Asociación Argentina de Nanomedicinas
Materia
HELMINTHS
ESSENTIAL OILS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/161199
Acceder
id CONICETDig_7a2ae68ca1cbd3471895c0c98306425c
oai_identifier_str oai:ri.conicet.gov.ar:11336/161199
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Behavioral and molecular bases of the anthelmintic activity of essential oils explored in the nematode Caenorhabditis elegansHernando, Guillermina SilvanaTurani, OrnellaBouzat, Cecilia BeatrizHELMINTHSESSENTIAL OILShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Control of helminth infections in both human and veterinary med icine currently relies mainly on chemotherapy, but acquisition of resistance is an increasing problem that leads to the urgent need of discovery of novel drugs. C. elegans has demonstrated to be a model system for the discovery of new anthelmintics and for char acterizing their mechanisms of action and resistance. Essential oils (EOs) are natural products produced by aromatic plants. We per form paralysis assays of wild-type and mutant C. elegans strain to identify EOs with potential anthelmintic activities, reveal the active components, their target sites, and mechanisms of action. We found that EOs belonging to different orders produce rapid paralysis of C. elegans with EC50 values between 0.02-2 % EOs. All EOs test ed also inhibited egg hatching, a property related to anthelmintic ability. Thus, EOs mediate both rapid and long-term anthelmintic effects. We examined anthelmintic properties of terpenoids and phenylpropenes and determined that all compounds tested produce both paralysis and egg-hatching inhibition. By testing mutant worms, we identified the muscle L-AChR and GABA receptors as EOs and trans-cinnamaldehyde (TC, phenylpropene) targets. Thus, by modulating two receptors with key roles in worm motility, these EOs emerge as novel sources of anthelmintic compounds. To unequivo cally confirm that these receptors are targets of TC and to describe the mechanism by which they affect these receptors, we performed whole-cell and single-channel recordings from C. elegans muscle cells. Electrophysiological recordings at the single-channel level re vealed that TC reduces L-AChR channel activity without affecting channel properties. The results are compatible with the action of these drugs as allosteric inhibitors. It is hoped that this work can update the recent progress on natural nematicide discoveries and provide new ideas for the design and mechanism of action studies of anthelmintics.Fil: Hernando, Guillermina Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Turani, Ornella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaLXVI Reunión anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión anual de la Sociedad Argentina de Immunología; LIII Reunión anual de la Asociación Argentina de Farmacología Experimental y XI Reunión anual de la Asociación Argentina de NanomedicinasArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaSociedad Argentina de Farmacología ExperimentalAsociación Argentina de NanomedicinasFundación Revista Medicina2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/161199Behavioral and molecular bases of the anthelmintic activity of essential oils explored in the nematode Caenorhabditis elegans; LXVI Reunión anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión anual de la Sociedad Argentina de Immunología; LIII Reunión anual de la Asociación Argentina de Farmacología Experimental y XI Reunión anual de la Asociación Argentina de Nanomedicinas; Argentina; 2021; 96-970025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicinaNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:29:11Zoai:ri.conicet.gov.ar:11336/161199instacron: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:34982025-10-15 15:29:12.119CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Behavioral and molecular bases of the anthelmintic activity of essential oils explored in the nematode Caenorhabditis elegans
title Behavioral and molecular bases of the anthelmintic activity of essential oils explored in the nematode Caenorhabditis elegans
spellingShingle Behavioral and molecular bases of the anthelmintic activity of essential oils explored in the nematode Caenorhabditis elegans
Hernando, Guillermina Silvana
HELMINTHS
ESSENTIAL OILS
title_short Behavioral and molecular bases of the anthelmintic activity of essential oils explored in the nematode Caenorhabditis elegans
title_full Behavioral and molecular bases of the anthelmintic activity of essential oils explored in the nematode Caenorhabditis elegans
title_fullStr Behavioral and molecular bases of the anthelmintic activity of essential oils explored in the nematode Caenorhabditis elegans
title_full_unstemmed Behavioral and molecular bases of the anthelmintic activity of essential oils explored in the nematode Caenorhabditis elegans
title_sort Behavioral and molecular bases of the anthelmintic activity of essential oils explored in the nematode Caenorhabditis elegans
dc.creator.none.fl_str_mv Hernando, Guillermina Silvana
Turani, Ornella
Bouzat, Cecilia Beatriz
author Hernando, Guillermina Silvana
author_facet Hernando, Guillermina Silvana
Turani, Ornella
Bouzat, Cecilia Beatriz
author_role author
author2 Turani, Ornella
Bouzat, Cecilia Beatriz
author2_role author
author
dc.subject.none.fl_str_mv HELMINTHS
ESSENTIAL OILS
topic HELMINTHS
ESSENTIAL OILS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Control of helminth infections in both human and veterinary med icine currently relies mainly on chemotherapy, but acquisition of resistance is an increasing problem that leads to the urgent need of discovery of novel drugs. C. elegans has demonstrated to be a model system for the discovery of new anthelmintics and for char acterizing their mechanisms of action and resistance. Essential oils (EOs) are natural products produced by aromatic plants. We per form paralysis assays of wild-type and mutant C. elegans strain to identify EOs with potential anthelmintic activities, reveal the active components, their target sites, and mechanisms of action. We found that EOs belonging to different orders produce rapid paralysis of C. elegans with EC50 values between 0.02-2 % EOs. All EOs test ed also inhibited egg hatching, a property related to anthelmintic ability. Thus, EOs mediate both rapid and long-term anthelmintic effects. We examined anthelmintic properties of terpenoids and phenylpropenes and determined that all compounds tested produce both paralysis and egg-hatching inhibition. By testing mutant worms, we identified the muscle L-AChR and GABA receptors as EOs and trans-cinnamaldehyde (TC, phenylpropene) targets. Thus, by modulating two receptors with key roles in worm motility, these EOs emerge as novel sources of anthelmintic compounds. To unequivo cally confirm that these receptors are targets of TC and to describe the mechanism by which they affect these receptors, we performed whole-cell and single-channel recordings from C. elegans muscle cells. Electrophysiological recordings at the single-channel level re vealed that TC reduces L-AChR channel activity without affecting channel properties. The results are compatible with the action of these drugs as allosteric inhibitors. It is hoped that this work can update the recent progress on natural nematicide discoveries and provide new ideas for the design and mechanism of action studies of anthelmintics.
Fil: Hernando, Guillermina Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Turani, Ornella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
LXVI Reunión anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión anual de la Sociedad Argentina de Immunología; LIII Reunión anual de la Asociación Argentina de Farmacología Experimental y XI Reunión anual de la Asociación Argentina de Nanomedicinas
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Farmacología Experimental
Asociación Argentina de Nanomedicinas
description Control of helminth infections in both human and veterinary med icine currently relies mainly on chemotherapy, but acquisition of resistance is an increasing problem that leads to the urgent need of discovery of novel drugs. C. elegans has demonstrated to be a model system for the discovery of new anthelmintics and for char acterizing their mechanisms of action and resistance. Essential oils (EOs) are natural products produced by aromatic plants. We per form paralysis assays of wild-type and mutant C. elegans strain to identify EOs with potential anthelmintic activities, reveal the active components, their target sites, and mechanisms of action. We found that EOs belonging to different orders produce rapid paralysis of C. elegans with EC50 values between 0.02-2 % EOs. All EOs test ed also inhibited egg hatching, a property related to anthelmintic ability. Thus, EOs mediate both rapid and long-term anthelmintic effects. We examined anthelmintic properties of terpenoids and phenylpropenes and determined that all compounds tested produce both paralysis and egg-hatching inhibition. By testing mutant worms, we identified the muscle L-AChR and GABA receptors as EOs and trans-cinnamaldehyde (TC, phenylpropene) targets. Thus, by modulating two receptors with key roles in worm motility, these EOs emerge as novel sources of anthelmintic compounds. To unequivo cally confirm that these receptors are targets of TC and to describe the mechanism by which they affect these receptors, we performed whole-cell and single-channel recordings from C. elegans muscle cells. Electrophysiological recordings at the single-channel level re vealed that TC reduces L-AChR channel activity without affecting channel properties. The results are compatible with the action of these drugs as allosteric inhibitors. It is hoped that this work can update the recent progress on natural nematicide discoveries and provide new ideas for the design and mechanism of action studies of anthelmintics.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/161199
Behavioral and molecular bases of the anthelmintic activity of essential oils explored in the nematode Caenorhabditis elegans; LXVI Reunión anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión anual de la Sociedad Argentina de Immunología; LIII Reunión anual de la Asociación Argentina de Farmacología Experimental y XI Reunión anual de la Asociación Argentina de Nanomedicinas; Argentina; 2021; 96-97
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/161199
identifier_str_mv Behavioral and molecular bases of the anthelmintic activity of essential oils explored in the nematode Caenorhabditis elegans; LXVI Reunión anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión anual de la Sociedad Argentina de Immunología; LIII Reunión anual de la Asociación Argentina de Farmacología Experimental y XI Reunión anual de la Asociación Argentina de Nanomedicinas; Argentina; 2021; 96-97
0025-7680
1669-9106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicina
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
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_ 1846083431637712896
score 13.22299

Publicaciones similares