title: South African plants used in traditional medicine to treat epilepsy have an antagonistic effect on NMDA receptor currents.
abstract: BACKGROUND
  Several Searsia species (Anacardiaceae), including Searsia dentata and Searsia pyroides, are used in South Africa traditional medicine to treat epilepsy. Ethanol leaf extracts of these plants have been shown to act as possible antagonists of N-methyl-d-aspartate (NMDA)-type glutamate receptors.
  
  
  METHODS
  Leaf material of three Searsia species were collected from the Botanical Garden at the University of KwaZulu-Natal, Pietermaritzburg; dried and extracted with ethanol in an ultrasound bath. Filtered and dried extracts were resuspended in DMSO (100mg/ml) and diluted in the recording solution. The effect of Searsia dentata, Searsia pyroides and Searsia glauca extracts was investigated in dissociated cerebellar granule cells (CGCs) from 8-day-old rats and in transiently transfected HEK (human embryonic kidney) 293 cells (HEK), expressing either NR1a/NR2A or NR1a/NR2B receptors. In both systems we measured whole-cell currents elicited by 0.5mM NMDA (CGCs) or 50 μM glutamic acid (HEK) at -60 mV in 0Mg and 30 μM glycine and NMDA driven Ca influx in Fura2-loaded CGC.
  
  
  RESULTS
  Searsia dentata and Searsia pyroides ethanol extracts caused a dose-dependent decrease of NR current with ED(50) close to 0.03 mg/ml in CGC and a similar inhibition (80% with 1mg/ml) in HEK cells, while Searsia glauca was much less effective. The inhibition was dependent on time of incubation and slightly favored by opening of the NR channel. It was hardly reversible during the recording time, but was not caused by accelerated run-down or by interaction with the modulatory redox site. Searsia pyroides ethanol extract also depressed the NMDA stimulated increase in intracellular Ca.
  
  
  CONCLUSIONS
  The data confirm the specificity of Searsia dentata and Searsia pyroides and justify their use in traditional medicine. These plants may combine one or more γ-aminobutyric acid (GABA)(A) agonists with one or more NMDA antagonists, thus representing an efficient treatment for epilepsy.
authors.affiliation: Institute of Biophysics, National Research Council, via De Marini 6, 16149 Genova, Italy. marchetti@ge.ibf.cnr.it
authors.forename: Carla
authors.initials: C
authors.lastname: Marchetti
authors.forename: Paola
authors.initials: P
authors.lastname: Gavazzo
authors.forename: Gary I
authors.initials: GI
authors.lastname: Stafford
authors.forename: Johannes
authors.initials: J
authors.lastname: Van Staden
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000737:chemistry; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D016488:Medicine, African Traditional; D008564:Membrane Potentials; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D029045:Rhus / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013997:Time Factors; D014162:Transfection
chemical_list: D000927:Anticonvulsants; D000431:Ethanol; D018691:Excitatory Amino Acid Antagonists; D010936:Plant Extracts; D016194:Receptors, N-Methyl-D-Aspartate; D012997:Solvents; C473649:NR1A NMDA receptor, rat; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor