Involvement of GABA/BDZ receptors in the anticonvulsant effects of dihydrosanguinarine from Bocconia arborea S. Watson

Bocconia arborea S. Watson (B. arborea) belongs to the Papaveraceae family and is used in folk medicine because of its depressant effect on the central nervous system. However, its benefits on cerebral paroxysmal activity as an anticonvulsant treatment remain unknown. This study aimed to evaluate th...

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Main Authors: José David González-Gómez, Samuel Estrada-Soto, Emmanuel Gaona-Tovar, María Eva González-Trujano, Benjamín Villasana-Salazar, Hugo Fernando Narváez-González, David Martínez-Vargas
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405844025010825
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author José David González-Gómez
Samuel Estrada-Soto
Emmanuel Gaona-Tovar
María Eva González-Trujano
Benjamín Villasana-Salazar
Hugo Fernando Narváez-González
David Martínez-Vargas
author_facet José David González-Gómez
Samuel Estrada-Soto
Emmanuel Gaona-Tovar
María Eva González-Trujano
Benjamín Villasana-Salazar
Hugo Fernando Narváez-González
David Martínez-Vargas
author_sort José David González-Gómez
collection DOAJ
description Bocconia arborea S. Watson (B. arborea) belongs to the Papaveraceae family and is used in folk medicine because of its depressant effect on the central nervous system. However, its benefits on cerebral paroxysmal activity as an anticonvulsant treatment remain unknown. This study aimed to evaluate the anticonvulsant effect of B. arborea and one of its abundant isolated metabolites dihydrosanguinarine (DHS) by means of experimental models of seizures in mice simultaneously to an electrocorticographic (ECoG) analysis. B. arborea was prepared as extracts with different polarity using hexane (HEX), dichloromethane (DCM), and methanol (MeOH) solvents to choose the most active one and to identify and isolate a bioactive metabolite. DHS was purified from the HEX extract. The anticonvulsant activity was evaluated with each extract giving an intraperitoneal (i.p.) administration of 100 mg/kg, and 30 min after, seizure behavior was induced by the pentylenetetrazole (PTZ, 85 mg/kg, i.p.) or maximal electroshock stimulation (MES) tests in mice. Molecular docking analysis was performance to reinforce the possible mechanism of action. Our results of seizure behavior and ECoG analysis showed that the HEX extract significantly (p < 0.0001) delayed the onset of seizures and decreased the incidence (p < 0.005) with lower mortality rate (p < 0.05), where DHS was partially responsible for this activity with a possible GABAergic mechanism of action involving the BDZ allosteric site. The MeOH extract also produced a significant effect (p < 0.05) but with less intensity than the HEX extract in the PTZ-induced seizures. A similar anticonvulsant response was observed in the MES test in the presence of DHS (p < 0.005) and the HEX extract (p < 0.05), but not in the case of the MeOH extract. In conclusion, our study provides evidence that non-polar and polar constituents of B. arborea participate in its anticonvulsant property, where DHS might play an important role in the therapy of convulsions mediated by GABAA/BDZ receptor modulation.
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spelling doaj-art-d9be3ca94d174995adf645980265c9eb2025-08-20T03:11:47ZengElsevierHeliyon2405-84402025-02-01114e4270110.1016/j.heliyon.2025.e42701Involvement of GABA/BDZ receptors in the anticonvulsant effects of dihydrosanguinarine from Bocconia arborea S. WatsonJosé David González-Gómez0Samuel Estrada-Soto1Emmanuel Gaona-Tovar2María Eva González-Trujano3Benjamín Villasana-Salazar4Hugo Fernando Narváez-González5David Martínez-Vargas6Laboratorio de Neurofisiología del Control y la Regulación, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz. Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, Ciudad de México 14370, MexicoFacultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, 62209, MexicoFacultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, 62209, MexicoLaboratorio de Neurofarmacología de Productos Naturales, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, Ciudad de México 14370, Mexico; Corresponding author.Laboratorio de Neurofisiología del Control y la Regulación, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz. Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, Ciudad de México 14370, MexicoHospital de Especialidades Dr. Belisario Domínguez, Av. Tláhuac 4866, San Lorenzo Tezonco, Iztapalapa, Ciudad de México 09930, Mexico; Centro Médico Nacional 20 de Noviembre, Félix Cuevas 540, Col del Valle Sur, Benito Juárez, 03104, Ciudad de México, MexicoLaboratorio de Neurofisiología del Control y la Regulación, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz. Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, Ciudad de México 14370, Mexico; Corresponding author.Bocconia arborea S. Watson (B. arborea) belongs to the Papaveraceae family and is used in folk medicine because of its depressant effect on the central nervous system. However, its benefits on cerebral paroxysmal activity as an anticonvulsant treatment remain unknown. This study aimed to evaluate the anticonvulsant effect of B. arborea and one of its abundant isolated metabolites dihydrosanguinarine (DHS) by means of experimental models of seizures in mice simultaneously to an electrocorticographic (ECoG) analysis. B. arborea was prepared as extracts with different polarity using hexane (HEX), dichloromethane (DCM), and methanol (MeOH) solvents to choose the most active one and to identify and isolate a bioactive metabolite. DHS was purified from the HEX extract. The anticonvulsant activity was evaluated with each extract giving an intraperitoneal (i.p.) administration of 100 mg/kg, and 30 min after, seizure behavior was induced by the pentylenetetrazole (PTZ, 85 mg/kg, i.p.) or maximal electroshock stimulation (MES) tests in mice. Molecular docking analysis was performance to reinforce the possible mechanism of action. Our results of seizure behavior and ECoG analysis showed that the HEX extract significantly (p < 0.0001) delayed the onset of seizures and decreased the incidence (p < 0.005) with lower mortality rate (p < 0.05), where DHS was partially responsible for this activity with a possible GABAergic mechanism of action involving the BDZ allosteric site. The MeOH extract also produced a significant effect (p < 0.05) but with less intensity than the HEX extract in the PTZ-induced seizures. A similar anticonvulsant response was observed in the MES test in the presence of DHS (p < 0.005) and the HEX extract (p < 0.05), but not in the case of the MeOH extract. In conclusion, our study provides evidence that non-polar and polar constituents of B. arborea participate in its anticonvulsant property, where DHS might play an important role in the therapy of convulsions mediated by GABAA/BDZ receptor modulation.http://www.sciencedirect.com/science/article/pii/S2405844025010825AlkaloidsBocconia arboreaDihydrosanguinarineElectrocorticogramSeizures
spellingShingle José David González-Gómez
Samuel Estrada-Soto
Emmanuel Gaona-Tovar
María Eva González-Trujano
Benjamín Villasana-Salazar
Hugo Fernando Narváez-González
David Martínez-Vargas
Involvement of GABA/BDZ receptors in the anticonvulsant effects of dihydrosanguinarine from Bocconia arborea S. Watson
Heliyon
Alkaloids
Bocconia arborea
Dihydrosanguinarine
Electrocorticogram
Seizures
title Involvement of GABA/BDZ receptors in the anticonvulsant effects of dihydrosanguinarine from Bocconia arborea S. Watson
title_full Involvement of GABA/BDZ receptors in the anticonvulsant effects of dihydrosanguinarine from Bocconia arborea S. Watson
title_fullStr Involvement of GABA/BDZ receptors in the anticonvulsant effects of dihydrosanguinarine from Bocconia arborea S. Watson
title_full_unstemmed Involvement of GABA/BDZ receptors in the anticonvulsant effects of dihydrosanguinarine from Bocconia arborea S. Watson
title_short Involvement of GABA/BDZ receptors in the anticonvulsant effects of dihydrosanguinarine from Bocconia arborea S. Watson
title_sort involvement of gaba bdz receptors in the anticonvulsant effects of dihydrosanguinarine from bocconia arborea s watson
topic Alkaloids
Bocconia arborea
Dihydrosanguinarine
Electrocorticogram
Seizures
url http://www.sciencedirect.com/science/article/pii/S2405844025010825
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