Anticonvulsant effect of kaurenoic acid isolated from the root bark of Annona senegalensis

• Root bark extracts of Annona senegalensis exhibited anticonvulsant effects.
• Kaurenoic acid is the anticonvulsant constituent in root bark of A. senegalensis.
• Kaurenoic acid exhibited activity against PTZ-induced seizures in mice.
• Hence kaurenoic acid by extrapolation may be a good candidate for absence seizures.
• The possible mechanism of KA is inhibition of GABAA-receptor chloride complex.

ContextThe 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.ObjectiveThe aim of this study was to identify and characterize the active constituent responsible for the anticonvulsant effect.Materials and methodsBioactive-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.ResultsThe 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).Discussion and conclusionKaurenoic 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.