title: Anticonvulsant activity of an active fraction extracted from Crinum jagus L. (Amaryllidaceae), and its possible effects on fully kindled seizures, depression-like behaviour and oxidative stress in experimental rodent models.
abstract: BACKGROUND
  The leaf extract of Crinum jagus L. (Amaryllidaceae) is widely used in traditional Cameroonian medicine as antiepileptic remedy and for the treatment of convulsion, depression and mood disorders associated with epilepsy.
  
  
  OBJECTIVE
  Hence, this study was conducted to evaluate the effects of an active fraction extracted from the leaves of Crinum jagus against seizures, depression-like behaviour and oxidative stress in pentylenetetrazole (PTZ)-induced kindling in mice.
  
  
  METHODS
  Bioactive-guided fractionation of the leaf extract of Crinum jagus by using 70mg/kg PTZ-induced convulsions in mice, afforded a potent anticonvulsant fraction (flavonol kaempferol; C4.4). The effects of C4.4 on 30mg/kg PTZ-induced kindling, kindling-induced depression like-behaviour and oxidative stress was evaluated. Mice were injected PTZ (30mg/kg, i.p.) once every alternate day (48±1h) until the development of kindling. Depression was assessed using tail suspension test and forced swim test while the oxidative stress parameters were estimated in the whole brain at the end of experiments. Mice were submitted to the rota-rod task and open-field test in order to assess any non-specific muscle-relaxant or sedative effects of C4.4. Acute toxicity of C4.4 was also assessed in mice.
  
  
  RESULTS
  Convulsions-induced by 70mg/kg PTZ were strongly antagonized by C4.4. Oral administration of C4.4 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 PTZ-kindled mice. The data indicated also that C4.4 significantly reduced the immobility times in the tail suspension test and the forced swim test. This active fraction has also antioxidant properties by decreasing the lipid peroxidation, and augmenting endogenous antioxidant enzymes in brain. C4.4 administered (12.5-50mg/kg) did not alter the locomotion of animals in the open-field or rotarod tests, which suggest a lack of a central depressant effect. The animals did not exhibit any acute toxicity to C4.4 at the therapeutic doses.
  
  
  CONCLUSIONS
  These results suggest that pretreatment with C4.4 ameliorates convulsions-induced by PTZ, protects mice against kindling development, depression-like behaviour and oxidative stress in PTZ-kindled mice. These finding provides scientific rationale for the use of Crinum jagus extracts for the amelioration of epilepsy observed in traditional medicine in Cameroon.
authors.affiliation: Department of Zoology and Animal Physiology, Faculty of Science, University of Buea, Buea , Cameroon. Electronic address: taiwe_sotoing@yahoo.fr.
authors.forename: Germain Sotoing
authors.initials: GS
authors.lastname: Taiwe
authors.affiliation: Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon.
authors.forename: Thierry Bang
authors.initials: TB
authors.lastname: Tchoya
authors.affiliation: Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon.
authors.forename: Joseph Renaud
authors.initials: JR
authors.lastname: Menanga
authors.affiliation: Department of Chemistry, Faculty of Science, University of Maroua, Maroua, Cameroon.
authors.forename: Bernard
authors.initials: B
authors.lastname: Dabole
authors.affiliation: Institut du Thorax, Inserm UMR 1087/CNRS UMR 6291, Nante, France; University of Nante, Nante, France; Smartox Biotechnology, Saint Martin d'Hères, France.
authors.forename: Michel
authors.initials: M
authors.lastname: De Waard
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D031407:Crinum / Q000737:chemistry*; D003863:Depression / Q000517:prevention & control*; D004195:Disease Models, Animal; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D010433:Pentylenetetrazole / Q000633:toxicity*; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D012640:Seizures / Q000517:prevention & control*
chemical_list: D000927:Anticonvulsants; D010936:Plant Extracts; D010433:Pentylenetetrazole
keywords: Crinum jagus; Depression; Epilepsy; Flavonol kaempferol; Oxidative stress