Original Investigation

Psychopharmacology

, Volume 197, Issue 3, pp 351-360

First online:

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 DuarteAffiliated withLaboratory of Neuropharmacology - Department of Pharmacology, Federal University of Santa Catarina
  • , Mariel MarderAffiliated withInstituto de Química y Fisicoquímica Biológicas - Faculdad de Farmacia y Bioquímica, University of Buenos Aires
  • , Alexandre Ademar HoellerAffiliated withLaboratory of Physiology—Department of Physiological Sciences, Federal University of Santa Catarina
  • , Marcelo DuzzioniAffiliated withLaboratory of Neuropharmacology - Department of Pharmacology, Federal University of Santa Catarina
  • , Beatriz Garcia MendesAffiliated withLaboratory of Organic Chemistry - Department of Chemistry, Federal University of Santa Catarina
  • , Moacir Geraldo PizzolattiAffiliated withLaboratory of Organic Chemistry - Department of Chemistry, Federal University of Santa Catarina
  • , Thereza Christina Monteiro De LimaAffiliated withLaboratory of Neuropharmacology - Department of Pharmacology, Federal University of Santa CatarinaDepartment of Pharmacology, Center of Biological Sciences, Federal University of Santa Catarina, Campus Universitário Email author 

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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 K i 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 (K d) and no change in maximal binding (B max).

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

Phytomedicines Polygala sabulosa Benzodiazepine site Anxiolytic Anticonvulsant