title: Kaempferol from the leaves of Apocynum venetum possesses anxiolytic activities in the elevated plus maze test in mice.
abstract: The present work evaluated the anxiolytic activity of an aqueous extract of Apocynum venetum L. (Apocynaceae) and bioguided its fractionation using the elevated plus maze (EPM) in mice as a model of anxiety. A single treatment of AV extract markedly increased the percentage time spent on the open arms of the EPM in two distinct concentration ranges of 22.5-30 and 100-125 mg/kg p.o., respectively, indicating a putative anxiolytic-like activity. Fractions showing anxiolytic effects in concentrations equal to 30 or 125 mg/kg of whole extract were antagonized using the benzodiazepine antagonist flumazenil (3 mg/kg i.p.) or the 5-HT(1A) receptor antagonist WAY-100635 (0.5 mg/kg i.p.). All active fractions in a concentration equal to 125 mg/kg were effectively blocked by the benzodiazepine antagonist flumazenil, while the anxiolytic activities of fractions in the lower dose equivalent to 30 mg/kg of whole extract were inhibited by the 5-HT(1A) receptor antagonist WAY-100635. Through further separation of AV fractions it was possible to isolate and characterize the flavonol kaempferol which showed an anxiolytic-like activity in concentrations from 0.02 to 1.0 mg/kg p.o. The anxiolytic activity of kaempferol was partially antagonized by concomitant administration of flumazenil, but not by WAY-100635. In conclusion, our study clearly demonstrates that AV extract possesses anxiolytic-like activity and that at least one of its flavonoids, kaempferol, can elicit the same kind of neuropharmacological activity.
authors.affiliation: College of Pharmacy, Department of Pharmaceutics, University of Florida, PO Box 100494, Gainesville, FL 32610, USA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Grundmann
authors.forename: Jun-Ichiro
authors.initials: J
authors.lastname: Nakajima
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kamata
authors.forename: Shujiro
authors.initials: S
authors.lastname: Seo
authors.forename: Veronika
authors.initials: V
authors.lastname: Butterweck
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy*; D030010:Apocynum; D001522:Behavior, Animal / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D044949:Kaempferols / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008517:Phytotherapy; D010879:Piperazines / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves; D011725:Pyridines / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid
chemical_list: D014151:Anti-Anxiety Agents; D018757:GABA Modulators; D044949:Kaempferols; D010879:Piperazines; D010936:Plant Extracts; D011725:Pyridines; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C006552:kaempferol; D003975:Diazepam