Data/hora: 22/06/2024 10:38:05

Biblioteca(s): 	Embrapa Florestas.	
Data corrente: 	29/05/2018	
Data da última atualização: 	30/05/2018	
Autoria: 	OLIVEIRA, D. R. de; TODO, A. H.; REGO, G. M.; CERUTTI, J. M.; CAVALHEIRO, A. J.; RANDO, D. G. G.; CERUTTI, S. M.	
Afiliação: 	Daniela Rodrigues de Oliveira, Universidade Federal de São Paulo; Andréia Hatsue Todo, Universidade Federal de São Paulo; GIZELDA MAIA REGO, CNPF; Janete Maria Cerutti, Universidade Federal de São Paulo; Alberto José Cavalheiro, UNESP; Daniela Gonçales Galasse Rando, Universidade Federal de São Paulo; Suzete Maria Cerutti, Universidade Federal de São Paulo.	
Título: 	Flavones-bound in benzodiazepine site on GABAA receptor: concomitant anxiolytic-like and cognitive-enhancing effects produced by Isovitexin and 6-C-glycoside-Diosmetin.	
Ano de publicação: 	2018	
Fonte/Imprenta: 	European Journal of Pharmacology, v. 831, p. 77-86, July 2018.	
DOI: 	10.1016/j.ejphar.2018.05.004	
Idioma: 	Inglês	
Conteúdo: 	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 30 min before training session with Vicenin-2 (0.1 and 0.25 mg/kg), Vitexin (0.1 and 0.25 mg/kg), Isovitexin (0.1 and 0.25 mg/kg) and 0.1 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 (P < 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 &#945;1His101 in the BZ-binding site on GABAA receptors, which may be related to memory-enhancing effect. The occurrence of the &#945;1His101 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.	
Palavras-Chave: 	Ácido gama aminobutírico; Ansiedade; Anxiety and memory; Efeito ansiolítico; GABA; GABAAR; Memória; Neurotransmissor; PM-DAT; Receptor.	
Thesagro: 	Erythrina Falcata; Farmacologia; Flavonóide.	
Thesaurus Nal: 	Flavones.	
Categoria do assunto: 	F Plantas e Produtos de Origem Vegetal	
Registro original: 	Embrapa Florestas (CNPF)	
Exemplares: 	CNPF - (56345-1) - UPC - AP - DD -  -  -  - DIS