Psychopharmacology

, Volume 197, Issue 3, pp 351–360

Anticonvulsant and anxiolytic-like effects of compounds isolated from Polygala sabulosa (Polygalaceae) in rodents: in vitro and in vivo interactions with benzodiazepine binding sites

  • Filipe Silveira Duarte
  • Mariel Marder
  • Alexandre Ademar Hoeller
  • Marcelo Duzzioni
  • Beatriz Garcia Mendes
  • Moacir Geraldo Pizzolatti
  • Thereza Christina Monteiro De Lima
Original Investigation

DOI: 10.1007/s00213-007-1037-z

Cite this article as:
Duarte, F.S., Marder, M., Hoeller, A.A. et al. Psychopharmacology (2008) 197: 351. doi:10.1007/s00213-007-1037-z

Abstract

Rationale

Polygala sabulosa, a folk medicine, presents dihydrostyryl-2-pyrones (DST) and styryl-2-pyrones (STY), compounds structurally similar to kavalactones. Our previous study showed that the ethyl acetate fraction (EA) and these constituents present anxiolytic-like, hypno-sedative, and anticonvulsant effects in mice.

Objectives

This study investigated the role of benzodiazepine binding site (BDZ-bs) in the central effects of either EA or three DST (1, 2, and 3) and three STY (4, 5, and 7), using in vivo and in vitro assays.

Methods and results

In the elevated plus-maze (EPM), flumazenil (FMZ), a BDZ antagonist, partially blocked the anxiolytic-like effect of DST-3 or STY-4 and STY-7, but not DST-1. Using electroencephalogram (EEG), EA protected against pentylenetetrazole (PTZ)-induced convulsion in rats, an effect partially blocked by FMZ, suggesting the participation of the BDZ-bs in this action. EA also protected against the maximal electroshock (MES)-induced convulsions in mice, a profile distinct from diazepam (DZP). DST and STY compounds inhibited the [3H]-flunitrazepam ([3H]-FNZ) binding to BDZ-bs in rat cortical synaptosomes with Ki higher than 100 μM (DST-1), 41.7 μM (DST-2), 35.8 μM (DST-3), 90.3 μM (STY-4), 31.0 μM (STY-5) and 70.0 μM (STY-7). In the saturation assay, DST-3 and STY-7 competitively inhibited the binding of [3H]-FNZ to BDZ-bs with a significant decrease in apparent affinity (Kd) and no change in maximal binding (Bmax).

Conclusions

The present data support a partial BDZ-bs mediation of the anxiolytic-like and anticonvulsant effects of EA of P. sabulosa and its main isolated constituents, DST and STY.

Keywords

PhytomedicinesPolygala sabulosaBenzodiazepine siteAnxiolyticAnticonvulsant

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Filipe Silveira Duarte
    • 1
  • Mariel Marder
    • 2
  • Alexandre Ademar Hoeller
    • 3
  • Marcelo Duzzioni
    • 1
  • Beatriz Garcia Mendes
    • 4
  • Moacir Geraldo Pizzolatti
    • 4
  • Thereza Christina Monteiro De Lima
    • 1
    • 5
  1. 1.Laboratory of Neuropharmacology - Department of PharmacologyFederal University of Santa CatarinaFlorianópolisBrazil
  2. 2.Instituto de Química y Fisicoquímica Biológicas - Faculdad de Farmacia y BioquímicaUniversity of Buenos AiresBuenos AiresArgentina
  3. 3.Laboratory of Physiology—Department of Physiological SciencesFederal University of Santa CatarinaFlorianópolisBrazil
  4. 4.Laboratory of Organic Chemistry - Department of ChemistryFederal University of Santa CatarinaFlorianópolisBrazil
  5. 5.Department of Pharmacology, Center of Biological Sciences, Federal University of Santa CatarinaCampus UniversitárioFlorianópolisBrazil