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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Flavones-bound in benzodiazepine site on GABA(A) receptor: Concomitant anxiolytic-like and cognitive-enhancing effects produced by Isovitexin and 6-C-glycoside-Diosmetin

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de Oliveira, Daniela Rodrigues [1, 2, 3] ; Todo, Andreia Hatsue [4] ; Rego, Gizelda Maia [5] ; Cerutti, Janete Maria [1] ; Cavalheiro, Alberto Jose [6] ; Galasse Rando, Daniela Goncales [4] ; Cerutti, Suzete Maria [2]
Total Authors: 7
[1] Univ Fed Sao Paulo, Dept Morfol & Genet, Lab Bases Genet Tumor Tiroide, Sao Paulo, SP - Brazil
[2] Univ Fed Sao Paulo, Dept Ciencias Biol, Lab Farmacol Celular & Comportamental, Diadema, SP - Brazil
[3] Univ Fed Sao Paulo, Dept Patol, Sao Paulo, SP - Brazil
[4] Univ Fed Sao Paulo, Dept Pharmaceut Sci, Med Chem Res Grp, Diadema, SP - Brazil
[5] Brazilian Agr Res Corp EMBRAPA, Dept Forestry Colombo, Colombo, Parana - Brazil
[6] Sao Paulo State Univ, Nuclei Bioassay Biosynth & Ecophysiol Nat Prod Nu, UNESP, Araraquara, SP - Brazil
Total Affiliations: 6
Document type: Journal article
Source: European Journal of Pharmacology; v. 831, p. 77-86, JUL 15 2018.
Web of Science Citations: 3

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 alpha 1His101 in the BZ-binding site on GABAA receptors, which may be related to memory-enhancing effect. The occurrence of the alpha 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. (AU)

FAPESP's process: 09/15229-8 - Expression of glutamatergic, serotoninergic and GABAergic receptors in the amygdala, hippocampus and prefrontal cortex of rats after acquisition and extinction of fear conditioning: potential therapeutic targets of the standardized extract of Ginkgo biloba
Grantee:Suzete Maria Cerutti
Support Opportunities: Regular Research Grants
FAPESP's process: 13/01875-0 - Parallel synthesis, in vitro screening and SAR studies of a nitroderivatives compounds library active against macrophage's pathogens: Mycobacterium tuberculosis NRP forms and Leishmania sp
Grantee:Daniela Goncales Galasse Rando
Support Opportunities: Regular Research Grants