title: Souroubea sympetala (Marcgraviaceae): a medicinal plant that exerts anxiolysis through interaction with the GABAA benzodiazepine receptor.
abstract: 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.
authors.affiliation: a Centre for Research in Biopharmaceuticals and Biotechnology, Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
authors.forename: Martha
authors.initials: M
authors.lastname: Mullally
authors.forename: Christian
authors.initials: C
authors.lastname: Cayer
authors.forename: Kari
authors.initials: K
authors.lastname: Kramp
authors.forename: Marco
authors.initials: M
authors.lastname: Otárola Rojas
authors.forename: Pablo
authors.initials: P
authors.lastname: Sanchez Vindas
authors.forename: Mario
authors.initials: M
authors.lastname: Garcia
authors.forename: Luis
authors.initials: L
authors.lastname: Poveda Alvarez
authors.forename: Tony
authors.initials: T
authors.lastname: Durst
authors.forename: Zul
authors.initials: Z
authors.lastname: Merali
authors.forename: Vance L
authors.initials: VL
authors.lastname: Trudeau
authors.forename: John T
authors.initials: JT
authors.lastname: Arnason
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000523:psychology; D005442:Flumazenil / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D008517:Phytotherapy; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D000094062:Betulinic Acid
chemical_list: D014151:Anti-Anxiety Agents; D005442:Flumazenil; D018755:GABA Agonists; D018756:GABA Antagonists; D010936:Plant Extracts; D011963:Receptors, GABA-A; D014315:Triterpenes; C534740:betulinic acid methyl ester; D000094062:Betulinic Acid
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