title: Anticonvulsant effect of kaurenoic acid isolated from the root bark of Annona senegalensis.
abstract: BACKGROUND
  The herbal preparations of Annona senegalensis Pers. (Annonaceae) root bark are used in Nigerian ethnomedicine for the treatment of epilepsy and febrile seizures. The scientific evidence for this effect has been reported.
  
  
  OBJECTIVE
  The aim of this study was to identify and characterize the active constituent responsible for the anticonvulsant effect.
  
  
  METHODS
  Bioactive-guided fractionation of the methanol-methylene chloride root bark extract (MME) of A. senegalensis using pentylenetetrazole (PTZ)-induced seizures in mice, afforded a potent anticonvulsant ethyl-acetate fraction (EF). Further fractionation of the EF yielded eight sub-fractions (F₁-F₈) which were tested for anticonvulsant activity. The sub-fraction F₂ yielded white crystals that were purified to obtain A. senegalensis crystals, AS2. The AS2, which exhibited potent anticonvulsant effects, was characterized by 1D and 2D NMR spectroscopy, mass spectroscopy and X-ray crystallography.
  
  
  RESULTS
  The AS2 was characterized as kaur-16-en-19-oic acid (KA), a diterpenoid. The AS2 indicated an oral LD₅₀ of 3800 mg/kg. The results showed that the MME, EF and AS2 significantly (P<0.05) and dose-dependently delayed the onset of myoclonic spasms and tonic-clonic phases of seizures induced by PTZ and maximal electroshock seizures (MES).
  
  
  CONCLUSIONS
  Kaurenoic acid was identified as the anticonvulsant principle in the root bark extract of A. senegalensis. The anticonvulsant effect of the MME, EF and AS2 is most likely being mediated through central inhibitory mechanisms.
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka 410001, Enugu State, Nigeria. theokuba@yahoo.com
authors.forename: Theophine C
authors.initials: TC
authors.lastname: Okoye
authors.forename: Peter A
authors.initials: PA
authors.lastname: Akah
authors.forename: Edwin O
authors.initials: EO
authors.lastname: Omeje
authors.forename: Festus B C
authors.initials: FB
authors.lastname: Okoye
authors.forename: Chukwuemeka S
authors.initials: CS
authors.lastname: Nworu
mesh_terms: D000818:Animals; D031041:Annona / Q000737:chemistry*; D000927:Anticonvulsants / Q000494:pharmacology*; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D024301:Plant Bark / Q000737:chemistry*; D051381:Rats; D045442:Rotarod Performance Test
chemical_list: D000927:Anticonvulsants; D004224:Diterpenes; C051436:kaurenoic acid