Kaempferol from the leaves of Apocynum venetum possesses anxiolytic activities in the elevated plus maze test in mice.
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.
Grundmann
Oliver
O
College of Pharmacy, Department of Pharmaceutics, University of Florida, PO Box 100494, Gainesville, FL 32610, USA.
Nakajima
Jun-Ichiro
J
Kamata
Kazuaki
K
Seo
Shujiro
S
Butterweck
Veronika
V
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
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