Unraveling anthelmintic targets and mechanisms of action of trans-cinnamaldehyde from cinnamon essential oil

Autores
Hernando, Guillermina Silvana; Turani, Ornella; Rodriguez Araujo, Noelia; Pulido Carrasquero, Alcibeth Yoselin; Bouzat, Cecilia Beatriz
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Parasitic nematodes pose a significant global socio-economic threat and contribute to neglected diseases. Current infection control relies on drug therapy, but increasing anthelmintic resistance highlights the urgent need for novel treatments. In this study, we investigate the molecular targets and mechanisms of action of trans-cinnamaldehyde (TCA), a principal component of Cinnamon Essential Oil (Cinnamomum verum EO), using Caenorhabditis elegans as a model organism. Our research offers new insights into the anthelmintic effects of TCA by identifying its specific interactions with key Cys-loop receptors and detailing its inhibitory mechanisms. The anthelmintic activity of C. verum EO and TCA manifests as rapid alterations in locomotor activity and inhibition of egg hatching. TCA screening of mutant worms lacking Cys-loop receptors reveal multiple receptor targets, including the levamisole-sensitive nicotinic ACh receptor (L-AChR), GABA-activated chloride channel (UNC-49) and glutamate-activated chloride channel. The mechanism behind the egg hatching inhibition by TCA remains unclear, as none of the mutants studied were found to be resistant to TCA. Furthermore, TCA increases the paralyzing effects of the anthelmintics levamisole and monepantel in a synergistic manner, offering a route for more effective polytherapy strategies. Electrophysiological studies on C. elegans Cys-loop receptors, in both native and heterologous systems, were used to elucidate the molecular mechanisms of TCA-induced paralysis. TCA reduces ACh- and GABA-elicited macroscopic currents and decreases single-channel activity and open durations of native muscle L-AChR channels, indicating an inhibitory action. Thus, by acting through a different mechanism to that of classical anthelmintics, TCA may be beneficial to counteract resistance in combined anthelmintic therapies. Our findings underscore the potential of the multitarget compound TCA as a valuable tool in integrated pharmacological strategies
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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Rodriguez Araujo, Noelia. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Pulido Carrasquero, Alcibeth Yoselin. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Materia
Cinnamomum verum essential oil
trans-cinnamaldehyde
anthelmintic drug
Cys-loop receptor
electrophysiology
Caenorhabditis elegans
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:11336/260019
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Unraveling anthelmintic targets and mechanisms of action of trans-cinnamaldehyde from cinnamon essential oilHernando, Guillermina SilvanaTurani, OrnellaRodriguez Araujo, NoeliaPulido Carrasquero, Alcibeth YoselinBouzat, Cecilia BeatrizCinnamomum verum essential oiltrans-cinnamaldehydeanthelmintic drugCys-loop receptorelectrophysiologyCaenorhabditis eleganshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Parasitic nematodes pose a significant global socio-economic threat and contribute to neglected diseases. Current infection control relies on drug therapy, but increasing anthelmintic resistance highlights the urgent need for novel treatments. In this study, we investigate the molecular targets and mechanisms of action of trans-cinnamaldehyde (TCA), a principal component of Cinnamon Essential Oil (Cinnamomum verum EO), using Caenorhabditis elegans as a model organism. Our research offers new insights into the anthelmintic effects of TCA by identifying its specific interactions with key Cys-loop receptors and detailing its inhibitory mechanisms. The anthelmintic activity of C. verum EO and TCA manifests as rapid alterations in locomotor activity and inhibition of egg hatching. TCA screening of mutant worms lacking Cys-loop receptors reveal multiple receptor targets, including the levamisole-sensitive nicotinic ACh receptor (L-AChR), GABA-activated chloride channel (UNC-49) and glutamate-activated chloride channel. The mechanism behind the egg hatching inhibition by TCA remains unclear, as none of the mutants studied were found to be resistant to TCA. Furthermore, TCA increases the paralyzing effects of the anthelmintics levamisole and monepantel in a synergistic manner, offering a route for more effective polytherapy strategies. Electrophysiological studies on C. elegans Cys-loop receptors, in both native and heterologous systems, were used to elucidate the molecular mechanisms of TCA-induced paralysis. TCA reduces ACh- and GABA-elicited macroscopic currents and decreases single-channel activity and open durations of native muscle L-AChR channels, indicating an inhibitory action. Thus, by acting through a different mechanism to that of classical anthelmintics, TCA may be beneficial to counteract resistance in combined anthelmintic therapies. Our findings underscore the potential of the multitarget compound TCA as a valuable tool in integrated pharmacological strategiesFil: 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; 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; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Rodriguez Araujo, Noelia. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Pulido Carrasquero, Alcibeth Yoselin. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; 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; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaSpringer Nature2025-02-13info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/260019Hernando, Guillermina Silvana; Turani, Ornella; Rodriguez Araujo, Noelia; Pulido Carrasquero, Alcibeth Yoselin; Bouzat, Cecilia Beatriz; Unraveling anthelmintic targets and mechanisms of action of trans-cinnamaldehyde from cinnamon essential oil; Springer Nature ; Scientific Reports; 15; 5422; 13-2-2025; 1-192045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-025-89883-4info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-025-89883-4info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:46:04Zoai:ri.conicet.gov.ar:11336/260019instacron: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 09:46:04.636CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Unraveling anthelmintic targets and mechanisms of action of trans-cinnamaldehyde from cinnamon essential oil
title Unraveling anthelmintic targets and mechanisms of action of trans-cinnamaldehyde from cinnamon essential oil
spellingShingle Unraveling anthelmintic targets and mechanisms of action of trans-cinnamaldehyde from cinnamon essential oil
Hernando, Guillermina Silvana
Cinnamomum verum essential oil
trans-cinnamaldehyde
anthelmintic drug
Cys-loop receptor
electrophysiology
Caenorhabditis elegans
title_short Unraveling anthelmintic targets and mechanisms of action of trans-cinnamaldehyde from cinnamon essential oil
title_full Unraveling anthelmintic targets and mechanisms of action of trans-cinnamaldehyde from cinnamon essential oil
title_fullStr Unraveling anthelmintic targets and mechanisms of action of trans-cinnamaldehyde from cinnamon essential oil
title_full_unstemmed Unraveling anthelmintic targets and mechanisms of action of trans-cinnamaldehyde from cinnamon essential oil
title_sort Unraveling anthelmintic targets and mechanisms of action of trans-cinnamaldehyde from cinnamon essential oil
dc.creator.none.fl_str_mv Hernando, Guillermina Silvana
Turani, Ornella
Rodriguez Araujo, Noelia
Pulido Carrasquero, Alcibeth Yoselin
Bouzat, Cecilia Beatriz
author Hernando, Guillermina Silvana
author_facet Hernando, Guillermina Silvana
Turani, Ornella
Rodriguez Araujo, Noelia
Pulido Carrasquero, Alcibeth Yoselin
Bouzat, Cecilia Beatriz
author_role author
author2 Turani, Ornella
Rodriguez Araujo, Noelia
Pulido Carrasquero, Alcibeth Yoselin
Bouzat, Cecilia Beatriz
author2_role author
author
author
author
dc.subject.none.fl_str_mv Cinnamomum verum essential oil
trans-cinnamaldehyde
anthelmintic drug
Cys-loop receptor
electrophysiology
Caenorhabditis elegans
topic Cinnamomum verum essential oil
trans-cinnamaldehyde
anthelmintic drug
Cys-loop receptor
electrophysiology
Caenorhabditis elegans
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Parasitic nematodes pose a significant global socio-economic threat and contribute to neglected diseases. Current infection control relies on drug therapy, but increasing anthelmintic resistance highlights the urgent need for novel treatments. In this study, we investigate the molecular targets and mechanisms of action of trans-cinnamaldehyde (TCA), a principal component of Cinnamon Essential Oil (Cinnamomum verum EO), using Caenorhabditis elegans as a model organism. Our research offers new insights into the anthelmintic effects of TCA by identifying its specific interactions with key Cys-loop receptors and detailing its inhibitory mechanisms. The anthelmintic activity of C. verum EO and TCA manifests as rapid alterations in locomotor activity and inhibition of egg hatching. TCA screening of mutant worms lacking Cys-loop receptors reveal multiple receptor targets, including the levamisole-sensitive nicotinic ACh receptor (L-AChR), GABA-activated chloride channel (UNC-49) and glutamate-activated chloride channel. The mechanism behind the egg hatching inhibition by TCA remains unclear, as none of the mutants studied were found to be resistant to TCA. Furthermore, TCA increases the paralyzing effects of the anthelmintics levamisole and monepantel in a synergistic manner, offering a route for more effective polytherapy strategies. Electrophysiological studies on C. elegans Cys-loop receptors, in both native and heterologous systems, were used to elucidate the molecular mechanisms of TCA-induced paralysis. TCA reduces ACh- and GABA-elicited macroscopic currents and decreases single-channel activity and open durations of native muscle L-AChR channels, indicating an inhibitory action. Thus, by acting through a different mechanism to that of classical anthelmintics, TCA may be beneficial to counteract resistance in combined anthelmintic therapies. Our findings underscore the potential of the multitarget compound TCA as a valuable tool in integrated pharmacological strategies
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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Rodriguez Araujo, Noelia. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Pulido Carrasquero, Alcibeth Yoselin. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
description Parasitic nematodes pose a significant global socio-economic threat and contribute to neglected diseases. Current infection control relies on drug therapy, but increasing anthelmintic resistance highlights the urgent need for novel treatments. In this study, we investigate the molecular targets and mechanisms of action of trans-cinnamaldehyde (TCA), a principal component of Cinnamon Essential Oil (Cinnamomum verum EO), using Caenorhabditis elegans as a model organism. Our research offers new insights into the anthelmintic effects of TCA by identifying its specific interactions with key Cys-loop receptors and detailing its inhibitory mechanisms. The anthelmintic activity of C. verum EO and TCA manifests as rapid alterations in locomotor activity and inhibition of egg hatching. TCA screening of mutant worms lacking Cys-loop receptors reveal multiple receptor targets, including the levamisole-sensitive nicotinic ACh receptor (L-AChR), GABA-activated chloride channel (UNC-49) and glutamate-activated chloride channel. The mechanism behind the egg hatching inhibition by TCA remains unclear, as none of the mutants studied were found to be resistant to TCA. Furthermore, TCA increases the paralyzing effects of the anthelmintics levamisole and monepantel in a synergistic manner, offering a route for more effective polytherapy strategies. Electrophysiological studies on C. elegans Cys-loop receptors, in both native and heterologous systems, were used to elucidate the molecular mechanisms of TCA-induced paralysis. TCA reduces ACh- and GABA-elicited macroscopic currents and decreases single-channel activity and open durations of native muscle L-AChR channels, indicating an inhibitory action. Thus, by acting through a different mechanism to that of classical anthelmintics, TCA may be beneficial to counteract resistance in combined anthelmintic therapies. Our findings underscore the potential of the multitarget compound TCA as a valuable tool in integrated pharmacological strategies
publishDate 2025
dc.date.none.fl_str_mv 2025-02-13
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/11336/260019
Hernando, Guillermina Silvana; Turani, Ornella; Rodriguez Araujo, Noelia; Pulido Carrasquero, Alcibeth Yoselin; Bouzat, Cecilia Beatriz; Unraveling anthelmintic targets and mechanisms of action of trans-cinnamaldehyde from cinnamon essential oil; Springer Nature ; Scientific Reports; 15; 5422; 13-2-2025; 1-19
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/260019
identifier_str_mv Hernando, Guillermina Silvana; Turani, Ornella; Rodriguez Araujo, Noelia; Pulido Carrasquero, Alcibeth Yoselin; Bouzat, Cecilia Beatriz; Unraveling anthelmintic targets and mechanisms of action of trans-cinnamaldehyde from cinnamon essential oil; Springer Nature ; Scientific Reports; 15; 5422; 13-2-2025; 1-19
2045-2322
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.nature.com/articles/s41598-025-89883-4
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-025-89883-4
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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eu_rights_str_mv openAccess
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dc.format.none.fl_str_mv application/pdf
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dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
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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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