Deciphering the molecular mechanisms underlying the anthelmintic effect of essential oils evaluated in 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
Helminths consist of a diverse group of parasitic worms including nematodes, which cause diseases of major socio-economic importance globally. Control of infections in both human and veterinary medicine currently relies mainly on chemotherapy, but acquisition of resistance is an increasing problem, so there is an urgent need for discovery of novel drugs. As parasitic nematodes are not ideal laboratory animals, C. elegans has demonstrated to be a model system for the discovery of new anthelmintics and for characterizing their mechanisms of action and resistance. Essential oils (EOs) are natural products produced by aromatic plants. We here perform 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 produced rapid paralysis of C. elegans showing EC50 values between 0.02-2 % of EOs. All EOs tested also inhibited egg hatching, a property related to anthelmintic ability. Thus, EOs mediate both rapid and long-term anthelmintic effects. Terpenoids are terpenes with added oxygen molecules, thymol and carvacrol are the most common and well-known terpenoids present in EOs. Phenylpropenes, such as eugenol and trans-cinnamaldehyde (TC), are named as such because they contain a six-carbon aromatic phenol group and a three-carbon propene tail from cinnamic acid. We determined that TC, produces both paralysis and egg-hatching inhibition. By testing mutant worms, we identified the muscle L-AChR and GABA receptors as EOs and TC targets. Thus, by modulating two receptors with key roles in worm motility, these EOs emerge as novel sources of anthelmintic compounds. To unequivocally 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 L1 C. elegans muscle cells. Electrophysiological recordings revealed that thymol, eugenol and carvacrol are not capable of eliciting macroscopic currents but they significantly reduce ACh- and GABA-elicited responses. At the single-channel level, we found that the activity of L-AChRs is significantly reduced in the presence of different terpenoids or phenylpropenes, without changes in channel properties. The results are compatible with the action of these drugs as allosteric inhibitors. Current studies are being carried out to determine if TC shows a similar action and to determine structure-activity relationships of the active compounds. 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. In addition, our study increases our knowledge related to the molecular function and pharmacology of the two main receptors involved in C. elegans locomotion
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
23rd International C. elegans Conference
Estados Unidos
Genetics Society of America
Materia
Caenorhabditis elegans
Anthelmintic effect
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:11336/162111

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network_name_str CONICET Digital (CONICET)
spelling Deciphering the molecular mechanisms underlying the anthelmintic effect of essential oils evaluated in Caenorhabditis elegansHernando, Guillermina SilvanaTurani, OrnellaBouzat, Cecilia BeatrizCaenorhabditis elegansAnthelmintic effecthttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Helminths consist of a diverse group of parasitic worms including nematodes, which cause diseases of major socio-economic importance globally. Control of infections in both human and veterinary medicine currently relies mainly on chemotherapy, but acquisition of resistance is an increasing problem, so there is an urgent need for discovery of novel drugs. As parasitic nematodes are not ideal laboratory animals, C. elegans has demonstrated to be a model system for the discovery of new anthelmintics and for characterizing their mechanisms of action and resistance. Essential oils (EOs) are natural products produced by aromatic plants. We here perform 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 produced rapid paralysis of C. elegans showing EC50 values between 0.02-2 % of EOs. All EOs tested also inhibited egg hatching, a property related to anthelmintic ability. Thus, EOs mediate both rapid and long-term anthelmintic effects. Terpenoids are terpenes with added oxygen molecules, thymol and carvacrol are the most common and well-known terpenoids present in EOs. Phenylpropenes, such as eugenol and trans-cinnamaldehyde (TC), are named as such because they contain a six-carbon aromatic phenol group and a three-carbon propene tail from cinnamic acid. We determined that TC, produces both paralysis and egg-hatching inhibition. By testing mutant worms, we identified the muscle L-AChR and GABA receptors as EOs and TC targets. Thus, by modulating two receptors with key roles in worm motility, these EOs emerge as novel sources of anthelmintic compounds. To unequivocally 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 L1 C. elegans muscle cells. Electrophysiological recordings revealed that thymol, eugenol and carvacrol are not capable of eliciting macroscopic currents but they significantly reduce ACh- and GABA-elicited responses. At the single-channel level, we found that the activity of L-AChRs is significantly reduced in the presence of different terpenoids or phenylpropenes, without changes in channel properties. The results are compatible with the action of these drugs as allosteric inhibitors. Current studies are being carried out to determine if TC shows a similar action and to determine structure-activity relationships of the active compounds. 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. In addition, our study increases our knowledge related to the molecular function and pharmacology of the two main receptors involved in C. elegans locomotionFil: 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; Argentina23rd International C. elegans ConferenceEstados UnidosGenetics Society of AmericaGenetics Society of AmericaAndrews, Brenda J. A.Lipshitz, Howard2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectConferenciaBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/162111Deciphering the molecular mechanisms underlying the anthelmintic effect of essential oils evaluated in Caenorhabditis elegans; 23rd International C. elegans Conference; Estados Unidos; 2021; 501-501CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://genetics-gsa.org/celegans-2021/program-and-abstract-books/Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:54:03Zoai:ri.conicet.gov.ar:11336/162111instacron: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:34982025-09-03 09:54:03.401CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Deciphering the molecular mechanisms underlying the anthelmintic effect of essential oils evaluated in Caenorhabditis elegans
title Deciphering the molecular mechanisms underlying the anthelmintic effect of essential oils evaluated in Caenorhabditis elegans
spellingShingle Deciphering the molecular mechanisms underlying the anthelmintic effect of essential oils evaluated in Caenorhabditis elegans
Hernando, Guillermina Silvana
Caenorhabditis elegans
Anthelmintic effect
title_short Deciphering the molecular mechanisms underlying the anthelmintic effect of essential oils evaluated in Caenorhabditis elegans
title_full Deciphering the molecular mechanisms underlying the anthelmintic effect of essential oils evaluated in Caenorhabditis elegans
title_fullStr Deciphering the molecular mechanisms underlying the anthelmintic effect of essential oils evaluated in Caenorhabditis elegans
title_full_unstemmed Deciphering the molecular mechanisms underlying the anthelmintic effect of essential oils evaluated in Caenorhabditis elegans
title_sort Deciphering the molecular mechanisms underlying the anthelmintic effect of essential oils evaluated in 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.contributor.none.fl_str_mv Andrews, Brenda J. A.
Lipshitz, Howard
dc.subject.none.fl_str_mv Caenorhabditis elegans
Anthelmintic effect
topic Caenorhabditis elegans
Anthelmintic effect
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Helminths consist of a diverse group of parasitic worms including nematodes, which cause diseases of major socio-economic importance globally. Control of infections in both human and veterinary medicine currently relies mainly on chemotherapy, but acquisition of resistance is an increasing problem, so there is an urgent need for discovery of novel drugs. As parasitic nematodes are not ideal laboratory animals, C. elegans has demonstrated to be a model system for the discovery of new anthelmintics and for characterizing their mechanisms of action and resistance. Essential oils (EOs) are natural products produced by aromatic plants. We here perform 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 produced rapid paralysis of C. elegans showing EC50 values between 0.02-2 % of EOs. All EOs tested also inhibited egg hatching, a property related to anthelmintic ability. Thus, EOs mediate both rapid and long-term anthelmintic effects. Terpenoids are terpenes with added oxygen molecules, thymol and carvacrol are the most common and well-known terpenoids present in EOs. Phenylpropenes, such as eugenol and trans-cinnamaldehyde (TC), are named as such because they contain a six-carbon aromatic phenol group and a three-carbon propene tail from cinnamic acid. We determined that TC, produces both paralysis and egg-hatching inhibition. By testing mutant worms, we identified the muscle L-AChR and GABA receptors as EOs and TC targets. Thus, by modulating two receptors with key roles in worm motility, these EOs emerge as novel sources of anthelmintic compounds. To unequivocally 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 L1 C. elegans muscle cells. Electrophysiological recordings revealed that thymol, eugenol and carvacrol are not capable of eliciting macroscopic currents but they significantly reduce ACh- and GABA-elicited responses. At the single-channel level, we found that the activity of L-AChRs is significantly reduced in the presence of different terpenoids or phenylpropenes, without changes in channel properties. The results are compatible with the action of these drugs as allosteric inhibitors. Current studies are being carried out to determine if TC shows a similar action and to determine structure-activity relationships of the active compounds. 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. In addition, our study increases our knowledge related to the molecular function and pharmacology of the two main receptors involved in C. elegans locomotion
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
23rd International C. elegans Conference
Estados Unidos
Genetics Society of America
description Helminths consist of a diverse group of parasitic worms including nematodes, which cause diseases of major socio-economic importance globally. Control of infections in both human and veterinary medicine currently relies mainly on chemotherapy, but acquisition of resistance is an increasing problem, so there is an urgent need for discovery of novel drugs. As parasitic nematodes are not ideal laboratory animals, C. elegans has demonstrated to be a model system for the discovery of new anthelmintics and for characterizing their mechanisms of action and resistance. Essential oils (EOs) are natural products produced by aromatic plants. We here perform 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 produced rapid paralysis of C. elegans showing EC50 values between 0.02-2 % of EOs. All EOs tested also inhibited egg hatching, a property related to anthelmintic ability. Thus, EOs mediate both rapid and long-term anthelmintic effects. Terpenoids are terpenes with added oxygen molecules, thymol and carvacrol are the most common and well-known terpenoids present in EOs. Phenylpropenes, such as eugenol and trans-cinnamaldehyde (TC), are named as such because they contain a six-carbon aromatic phenol group and a three-carbon propene tail from cinnamic acid. We determined that TC, produces both paralysis and egg-hatching inhibition. By testing mutant worms, we identified the muscle L-AChR and GABA receptors as EOs and TC targets. Thus, by modulating two receptors with key roles in worm motility, these EOs emerge as novel sources of anthelmintic compounds. To unequivocally 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 L1 C. elegans muscle cells. Electrophysiological recordings revealed that thymol, eugenol and carvacrol are not capable of eliciting macroscopic currents but they significantly reduce ACh- and GABA-elicited responses. At the single-channel level, we found that the activity of L-AChRs is significantly reduced in the presence of different terpenoids or phenylpropenes, without changes in channel properties. The results are compatible with the action of these drugs as allosteric inhibitors. Current studies are being carried out to determine if TC shows a similar action and to determine structure-activity relationships of the active compounds. 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. In addition, our study increases our knowledge related to the molecular function and pharmacology of the two main receptors involved in C. elegans locomotion
publishDate 2021
dc.date.none.fl_str_mv 2021
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info:eu-repo/semantics/conferenceObject
Conferencia
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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/11336/162111
Deciphering the molecular mechanisms underlying the anthelmintic effect of essential oils evaluated in Caenorhabditis elegans; 23rd International C. elegans Conference; Estados Unidos; 2021; 501-501
CONICET Digital
CONICET
url http://hdl.handle.net/11336/162111
identifier_str_mv Deciphering the molecular mechanisms underlying the anthelmintic effect of essential oils evaluated in Caenorhabditis elegans; 23rd International C. elegans Conference; Estados Unidos; 2021; 501-501
CONICET Digital
CONICET
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language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://genetics-gsa.org/celegans-2021/program-and-abstract-books/
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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 Internacional
dc.publisher.none.fl_str_mv Genetics Society of America
publisher.none.fl_str_mv Genetics Society of America
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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