02929naa a2200373 a 450000100080000000500110000800800410001902400380006010000230009824501960012126000090031752018120032665000130213865000220215165000170217365000160219065300310220665300140223765300230225165300240227465300090229865300110230765300130231865300210233165300110235265300130236370000160237670000160239270000190240870000220242770000200244970000190246977300670248820920462018-05-30       2018    bl uuuu     u00u1 u    #d7 a10.1016/j.ejphar.2018.05.0042DOI1 aOLIVEIRA, D. R. de  aFlavones-bound in benzodiazepine site on GABAA receptorbconcomitant anxiolytic-like and cognitive-enhancing effects produced by Isovitexin and 6-C-glycoside-Diosmetin.h[electronic resource]  c2018  aIncreasing 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 &lt 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.  aFlavones  aErythrina Falcata  aFarmacologia  aFlavonóide  aÁcido gama aminobutírico  aAnsiedade  aAnxiety and memory  aEfeito ansiolítico  aGABA  aGABAAR  aMemória  aNeurotransmissor  aPM-DAT  aReceptor1 aTODO, A. H.1 aREGO, G. M.1 aCERUTTI, J. M.1 aCAVALHEIRO, A. J.1 aRANDO, D. G. G.1 aCERUTTI, S. M.  tEuropean Journal of Pharmacologygv. 831, p. 77-86, July 2018.