“Central depressant action of flavonoid glycosides”

FERNÁNDEZ, SEBASTIÁN P.; WASOWSKI, CRISTINA; LOSCALZO, LEONARDO; PALADINI, ALEJANDRO C.; MARDER, MARIEL

Pinamar, Argentina

Congreso; X PABMB Congress-Panamerican Association for Biochemistry and Molecular Biology, SAIB, XLI Annual Meeting Sociedad Argentina de Investigación en Bioquímica y Biología Molecular y SAN, XX Annual Meeting Sociedad Argentina de Neuroquímica; 2005

PABMB, SAIB y SAN

Anxiety, depression and insomnia are very common mental disorders; the efficacy of present treatments is frequently diminished by side effects. We have demonstrated that some flavonoids possess affinity for the central benzodiazepine binding site of the GABAA receptor, and exert anxiolytic but not depressant effects in rodents. Recently we identified in valerian extracts two flavonoid glycosides, hesperidin and linarin, with sedative and sleep-enhancing activities in mice. The aim of the present work was to establish the structure-activity relationship for several flavonoid glycosides using different behavioral assays: locomotor activity, hole board exploration and thiopental-induced sleeping time. The possible role of GABAA receptors in these effects was explored by flunitrazepam and TBOB binding experiments, picrotoxin antagonism in vivo and electrophysiological assays in oocytes expressing GABAA receptors. The results suggest that flavonoid glycosides exert sedative and sleep-enhancing activities with a mechanism not involving GABAA system. Hesperidin is the most active compound assayed and any change of its structure decreases or suppresses activity