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


OBJECTIVE
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.


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 [(3)H]-flunitrazepam ([(3)H]-FNZ) binding to BDZ-bs in rat cortical synaptosomes with K (i) higher than 100 microM (DST-1), 41.7 microM (DST-2), 35.8 microM (DST-3), 90.3 microM (STY-4), 31.0 microM (STY-5) and 70.0 microM (STY-7). In the saturation assay, DST-3 and STY-7 competitively inhibited the binding of [(3)H]-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.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D000927:Anticonvulsants / Q000302:isolation & purification* / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D004597:Electroshock; D005239:Fear / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D010433:Pentylenetetrazole; D010936:Plant Extracts / Q000302:isolation & purification* / Q000494:pharmacology*; D031801:Polygala / Q000737:chemistry*; D011753:Pyrones / Q000302:isolation & purification* / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D010936:Plant Extracts; D011753:Pyrones; D011963:Receptors, GABA-A; D010433:Pentylenetetrazole