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Souroubea sympetala (Marcgraviaceae): a medicinal plant that exerts anxiolysis through interaction with the GABAA benzodiazepine receptor

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The mode of action of the anxiolytic medicinal plant Souroubea sympetala was investigated to test the hypothesis that extracts and the active principle act at the pharmacologically important GABAA–benzodiazepine (GABAA–BZD) receptor. Leaf extracts prepared by ethyl acetate extraction or supercritical extraction, previously determined to have 5.54 mg/g and 6.78 mg/g of the active principle, betulinic acid, respectively, reduced behavioural parameters associated with anxiety in a rat model. When animals were pretreated with the GABAA–BZD receptor antagonist flumazenil, followed by the plant extracts, or a more soluble derivative of the active principle, the methyl ester of betulinic acid (MeBA), flumazenil eliminated the anxiety-reducing effect of plant extracts and MeBA, demonstrating that S. sympetala acts via an agonist action on the GABAA–BZD receptor. An in vitro GABAA–BZD competitive receptor binding assay also demonstrated that S. sympetala extracts have an affinity for the GABAA–BZD receptor, with an EC50 value of 123 μg/mL (EtOAc leaf extract) and 154 μg/mL (supercritical CO2 extract). These experiments indicate that S. sympetala acts at the GABAA–BZD receptor to elicit anxiolysis.
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Keywords: acide bétulinique; anxiety; anxiété; betulinic acid; ester de méthyle d’acide bétulinique; methyl ester of betulinic acid; natural health product; pharmacologie; pharmacology; produit de santé naturel

Document Type: Research Article

Affiliations: 1: Centre for Research in Biopharmaceuticals and Biotechnology, Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada. 2: Universidad Nacional, Heredia, Costa Rica. 3: Department of Chemistry, University of Ottawa, Ottawa, ON K1N 6N5, Canada. 4: University of Ottawa Institute of Mental Health Research, School of Psychology and Departments of Cellular Medicine and Psychiatry, Ottawa, ON K1N 6N5, Canada. 5: Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada.

Publication date: January 1, 2014

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