Flavones-bound in benzodiazepine site on GABAA receptor: Concomitant anxiolytic-like and cognitive-enhancing effects produced by Isovitexin and 6-C-glycoside-Diosmetin.
Eur J Pharmacol
; 831: 77-86, 2018 Jul 15.
Article
en En
| MEDLINE
| ID: mdl-29738701
ABSTRACT
Increasing evidence suggests that flavones can modulate memory and anxiety-like behaviour. However, these therapeutic effects are inconsistent and induce of adverse effects, which have been associated with interactions at the Benzodiazepine (BZ)-binding site. To improve our understanding of flavone effects on memory and anxiety, we employed a plus-maze discriminative avoidance task. Furthermore, we evaluated the potential of the compounds in modulating GABAA receptors via BZ-binding site using molecular modelling studies. Adult male Wistar rats were treated 30â¯min before training session with Vicenin-2 (0.1 and 0.25â¯mg/kg), Vitexin (0.1 and 0.25â¯mg/kg), Isovitexin (0.1 and 0.25â¯mg/kg) and 0.1â¯mg/kg 6-C-glycoside-Diosmetin, vehicle and a GABAA receptor agonist. The analysis of the time spent in the non-aversive vs aversive enclosed arms during the test session and percentage of time in the open arms within the training session revealed that treatment with Isovitexin and 6-C-glycoside-Diosmetin had memory-enhancing and anxiolytic-like effects (Pâ¯<â¯0.001). In contrast, treatment with a higher dose of Diazepam impaired short-and long-term memory when it alleviated anxiety level. Docking studies revealed that flavones docked in a very similar way to that observed to the Diazepam, except by a lack of interaction in residue α1His101 in the BZ-binding site on GABAA receptors, which may be related to memory-enhancing effect. The occurrence of the α1His101 interaction could justify the memory-impairing observed following Diazepam treatment. These findings provide the first evidence that Isovitexin and 6-C-glycoside-Diosmetin could exert their memory-enhancing and anxiolytic-like effects via GABAA receptor modulation, which likely occurs via their benzodiazepine-binding site.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Ansiolíticos
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Conducta Animal
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Flavonoides
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Encéfalo
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Cognición
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Receptores de GABA-A
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Nootrópicos
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Apigenina
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Diazepam
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2018
Tipo del documento:
Article