Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8528998 | European Journal of Pharmacology | 2018 | 10 Pages |
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.
Related Topics
Life Sciences
Neuroscience
Cellular and Molecular Neuroscience
Authors
Daniela Rodrigues de Oliveira, Andréia Hatsue Todo, Gizelda Maia Rêgo, Janete Maria Cerutti, Alberto José Cavalheiro, Daniela Gonçales Galasse Rando, Suzete Maria Cerutti,