Cargando…

Antiseizure Effects of Scoparone, Borneol and Their Impact on the Anticonvulsant Potency of Four Classic Antiseizure Medications in the Mouse MES Model—An Isobolographic Transformation

Numerous botanical drugs containing coumarins and terpenes are used in ethnomedicine all over the world for their various therapeutic properties, especially those affecting the CNS system. The treatment of epilepsy is based on antiseizure medications (ASMs), although novel strategies using naturally...

Descripción completa

Detalles Bibliográficos
Autores principales: Łuszczki, Jarogniew J., Bojar, Hubert, Góralczyk, Agnieszka, Skalicka-Woźniak, Krystyna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9867083/
https://www.ncbi.nlm.nih.gov/pubmed/36674911
http://dx.doi.org/10.3390/ijms24021395
_version_ 1784876254529323008
author Łuszczki, Jarogniew J.
Bojar, Hubert
Góralczyk, Agnieszka
Skalicka-Woźniak, Krystyna
author_facet Łuszczki, Jarogniew J.
Bojar, Hubert
Góralczyk, Agnieszka
Skalicka-Woźniak, Krystyna
author_sort Łuszczki, Jarogniew J.
collection PubMed
description Numerous botanical drugs containing coumarins and terpenes are used in ethnomedicine all over the world for their various therapeutic properties, especially those affecting the CNS system. The treatment of epilepsy is based on antiseizure medications (ASMs), although novel strategies using naturally occurring substances with confirmed antiseizure properties are being developed nowadays. The aim of this study was to determine the anticonvulsant profiles of scoparone (a simple coumarin) and borneol (a bicyclic monoterpenoid) when administered separately and in combination, as well as their impact on the antiseizure effects of four classic ASMs (carbamazepine, phenytoin, phenobarbital and valproate) in the mouse model of maximal electroshock-induced (MES) tonic-clonic seizures. MES-induced seizures were evoked in mice receiving the respective doses of the tested natural compounds and classic ASMs (when applied alone or in combinations). Interactions for two-drug and three-drug mixtures were assessed by means of isobolographic transformation of data. Polygonograms were used to illustrate the types of interactions occurring among drugs. The total brain content of ASMs was measured in mice receiving the respective drug treatments with fluorescent polarization immunoassay. Scoparone and borneol, when administered alone, exerted anticonvulsant properties in the mouse MES model. The two-drug mixtures of scoparone with valproate, borneol with phenobarbital and borneol with valproate produced synergistic interactions in the mouse MES model, while the remaining tested two-drug mixtures produced additivity. The three-drug mixtures of scoparone + borneol with valproate and phenobarbital produced synergistic interactions in the mouse MES model. Verification of total brain concentrations of valproate and phenobarbital revealed that borneol elevated the total brain concentrations of both ASMs, while scoparone did not affect the brain content of these ASMs in mice. The synergistic interaction of scoparone with valproate observed in the mouse MES model is pharmacodynamic in nature. Borneol elevated the brain concentrations of the tested ASMs, contributing to the pharmacokinetic nature of the observed synergistic interactions with valproate and phenobarbital in the mouse MES model.
format Online
Article
Text
id pubmed-9867083
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-98670832023-01-22 Antiseizure Effects of Scoparone, Borneol and Their Impact on the Anticonvulsant Potency of Four Classic Antiseizure Medications in the Mouse MES Model—An Isobolographic Transformation Łuszczki, Jarogniew J. Bojar, Hubert Góralczyk, Agnieszka Skalicka-Woźniak, Krystyna Int J Mol Sci Article Numerous botanical drugs containing coumarins and terpenes are used in ethnomedicine all over the world for their various therapeutic properties, especially those affecting the CNS system. The treatment of epilepsy is based on antiseizure medications (ASMs), although novel strategies using naturally occurring substances with confirmed antiseizure properties are being developed nowadays. The aim of this study was to determine the anticonvulsant profiles of scoparone (a simple coumarin) and borneol (a bicyclic monoterpenoid) when administered separately and in combination, as well as their impact on the antiseizure effects of four classic ASMs (carbamazepine, phenytoin, phenobarbital and valproate) in the mouse model of maximal electroshock-induced (MES) tonic-clonic seizures. MES-induced seizures were evoked in mice receiving the respective doses of the tested natural compounds and classic ASMs (when applied alone or in combinations). Interactions for two-drug and three-drug mixtures were assessed by means of isobolographic transformation of data. Polygonograms were used to illustrate the types of interactions occurring among drugs. The total brain content of ASMs was measured in mice receiving the respective drug treatments with fluorescent polarization immunoassay. Scoparone and borneol, when administered alone, exerted anticonvulsant properties in the mouse MES model. The two-drug mixtures of scoparone with valproate, borneol with phenobarbital and borneol with valproate produced synergistic interactions in the mouse MES model, while the remaining tested two-drug mixtures produced additivity. The three-drug mixtures of scoparone + borneol with valproate and phenobarbital produced synergistic interactions in the mouse MES model. Verification of total brain concentrations of valproate and phenobarbital revealed that borneol elevated the total brain concentrations of both ASMs, while scoparone did not affect the brain content of these ASMs in mice. The synergistic interaction of scoparone with valproate observed in the mouse MES model is pharmacodynamic in nature. Borneol elevated the brain concentrations of the tested ASMs, contributing to the pharmacokinetic nature of the observed synergistic interactions with valproate and phenobarbital in the mouse MES model. MDPI 2023-01-11 /pmc/articles/PMC9867083/ /pubmed/36674911 http://dx.doi.org/10.3390/ijms24021395 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Łuszczki, Jarogniew J.
Bojar, Hubert
Góralczyk, Agnieszka
Skalicka-Woźniak, Krystyna
Antiseizure Effects of Scoparone, Borneol and Their Impact on the Anticonvulsant Potency of Four Classic Antiseizure Medications in the Mouse MES Model—An Isobolographic Transformation
title Antiseizure Effects of Scoparone, Borneol and Their Impact on the Anticonvulsant Potency of Four Classic Antiseizure Medications in the Mouse MES Model—An Isobolographic Transformation
title_full Antiseizure Effects of Scoparone, Borneol and Their Impact on the Anticonvulsant Potency of Four Classic Antiseizure Medications in the Mouse MES Model—An Isobolographic Transformation
title_fullStr Antiseizure Effects of Scoparone, Borneol and Their Impact on the Anticonvulsant Potency of Four Classic Antiseizure Medications in the Mouse MES Model—An Isobolographic Transformation
title_full_unstemmed Antiseizure Effects of Scoparone, Borneol and Their Impact on the Anticonvulsant Potency of Four Classic Antiseizure Medications in the Mouse MES Model—An Isobolographic Transformation
title_short Antiseizure Effects of Scoparone, Borneol and Their Impact on the Anticonvulsant Potency of Four Classic Antiseizure Medications in the Mouse MES Model—An Isobolographic Transformation
title_sort antiseizure effects of scoparone, borneol and their impact on the anticonvulsant potency of four classic antiseizure medications in the mouse mes model—an isobolographic transformation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9867083/
https://www.ncbi.nlm.nih.gov/pubmed/36674911
http://dx.doi.org/10.3390/ijms24021395
work_keys_str_mv AT łuszczkijarogniewj antiseizureeffectsofscoparoneborneolandtheirimpactontheanticonvulsantpotencyoffourclassicantiseizuremedicationsinthemousemesmodelanisobolographictransformation
AT bojarhubert antiseizureeffectsofscoparoneborneolandtheirimpactontheanticonvulsantpotencyoffourclassicantiseizuremedicationsinthemousemesmodelanisobolographictransformation
AT goralczykagnieszka antiseizureeffectsofscoparoneborneolandtheirimpactontheanticonvulsantpotencyoffourclassicantiseizuremedicationsinthemousemesmodelanisobolographictransformation
AT skalickawozniakkrystyna antiseizureeffectsofscoparoneborneolandtheirimpactontheanticonvulsantpotencyoffourclassicantiseizuremedicationsinthemousemesmodelanisobolographictransformation