The effect of extracts of Searsia species on epileptiform activity in slices of the mouse cerebral cortex.
BACKGROUND
Searsia dentata and Searsia pyroides are used in traditional South African medicine to treat convulsions and epilepsy. Previous studies have demonstrated that extracts of these plants comprise compounds that bind to the flumazenil-sensitive site on the GABA(A) receptor. However, their use as anticonvulsant medicinal plants cannot be adequately explained by these findings.


OBJECTIVE
The aim of this study was to examine the possible involvement of the glutamatergic system of extracts from the plants.


METHODS
The mouse cortical wedge preparation was used for functional characterization of the extracts. The affinity towards the NMDA and the AMPA receptor was investigated using classical [(3)H]-GP39653 and [(3)H]-AMPA binding assays, respectively.


RESULTS
The extracts of Searsia dentata and Searsia pyroides inhibited the spontaneous epileptiform discharges in mouse cerebral cortical slices with ED(50) of 0.62 and 1.67mg dry extract/mL, respectively. Both extracts displaced [(3)H]-GP39653 binding and significantly inhibited the NMDA-induced response during co-administration in cortical slices.


CONCLUSIONS
In this study, the NMDA receptor antagonistic effect of the crude ethanolic extracts of these two South African medicinal plants was demonstrated.
Pedersen
Mikael Egebjerg
ME
Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, 2 Universitetsparken, 2100 Copenhagen O, Denmark.
Vestergaard
Henrik Tang
HT
Stafford
Gary Ivan
GI
van Staden
Johannes
J
Jäger
Anna K
AK
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D016488:Medicine, African Traditional; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D018079:Receptors, GABA / Q000187:drug effects; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D029045:Rhus / Q000737:chemistry*; D013019:South Africa
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D007202:Indicators and Reagents; D010936:Plant Extracts; D018091:Receptors, AMPA; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C069052:CGP 39653; D015763:2-Amino-5-phosphonovalerate