title: Anticonvulsant effects of iridoid glycosides fraction purified from Feretia apodanthera Del. (Rubiaceae) in experimental mice models of generalized tonic-clonic seizures.
abstract: BACKGROUND
  Despite the increasing number and variety of antiepileptic drugs, nearly 30 % of epileptic patients who receive appropriate medical attention have persisting seizures. Anticonvulsant activity has been demonstrated for different iridoid glycoside-rich plant extracts. This study was designed to investigate the anticonvulsant effects of iridoid glycosides purified from Feretia apodanthera and to explore the possible mechanisms involved in antiepileptic activity.
  
  
  METHODS
  The anticonvulsant effects of iridoid glycosides extracts were investigated against 2.7 mg/kg bicuculline- and 70 mg/kg pentylenetetrazole-induced convulsions. The behavioural and electroencephalographic manifestations of 50 mg/kg pentylenetetrazole-induced seizures in mice as a model of generalized tonic-clonic seizures were also evaluated. Finally, the extracts were tested on the course of kindling development, kindled-seizures and oxidative stress markers in 30 mg/kg pentylenetetrazole-kindled mice. Their effects on brain GABA content were also determined.
  
  
  RESULTS
  The iridoid glycosides (30-90 mg/kg) protected mice against bicuculline-induced motor seizures in all pre-treated animals. Behavioural seizures- and mortality-induced by 70 mg/kg pentylenetetrazole were strongly antagonized by the extracts (60-90 mg/kg). The number of crisis (n/20 min), the cumulative duration of crisis (sec/20 min), and the mean duration of crisis (sec) recorded in 50 mg/kg pentylenetetrazole-treated mice were significantly decreased in all pre-treated mice with the extracts (60-90 mg/kg). Administration of the extracts (30-90 mg/kg) significantly increased the latency to myoclonic jerks, clonic seizures as well as generalized tonic-clonic seizures, improved the seizure mean stage and decreased the number of myoclonic jerks in 30 mg/kg pentylenetetrazole-kindled mice. Pentylenetetrazole kindling induced significant oxidative stress and brain GABA content alteration that was reversed by pretreatment with the extracts in a dose-dependent manner.
  
  
  CONCLUSIONS
  The results indicate that pretreatment with the iridoid glycosides extracts of Feretia apodenthera improves generalized tonic-clonic seizures-induced by chemo-convulsants, protects mice against kindling development and oxidative stress, and improves brain GABA content in pentylenetetrazole-kindled mice.
authors: Department of Zoology and Animal Physiology, Faculty of Science, University of Buea, Buea, Cameroon. taiwe_sotoing@yahoo.fr.
authors: Germain Sotoing
authors: GS
authors: Taiwe
authors: Department of Chemistry, Faculty of Science, University of Maroua, Maroua, Cameroon.
authors: Bernard
authors: B
authors: Dabole
authors: Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon.
authors: Thierry Bang
authors: TB
authors: Tchoya
authors: Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon.
authors: Joseph Renaud
authors: JR
authors: Menanga
authors: Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon.
authors: Paul Désiré Djomeni
authors: PD
authors: Dzeufiet
authors: Institut du Thorax, Inserm UMR 1087/CNRS UMR 6291, Nante, France.|University of Nante, Nante, France.|Smartox Biotechnology, Saint Martin d'Hères, France.
authors: Michel
authors: M
authors: De Waard
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D005978:Glutathione / Q000032:analysis; D057889:Iridoid Glycosides / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole / Q000633:toxicity; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D019666:Rubiaceae / Q000737:chemistry*; D012640:Seizures / Q000139:chemically induced*
chemical_list: D000927:Anticonvulsants; D057889:Iridoid Glycosides; D010936:Plant Extracts; D005978:Glutathione; D010433:Pentylenetetrazole
keywords: Antiepileptic drugs; Iridoid glycosides; Kindling development; Oxidative stress; Tonic-clonic seizures