Anticonvulsant effect of methanolic extract and isolation of active constituents from Cnestis ferruginea Vahl ex DC (Connaraceae)

Background: The root decoction of Cnestis ferruginea Vahl ex DC (Connaraceae) is used in traditional African medicine (TAM) in the treatment of epilepsy. Objectives: This study sought to investigate the anticonvulsant effect of the methanolic root extract of Cnestis ferruginea (CF) in mice as well as isolation of its phytoconstituents responsible for the observed effect . Methods: Anticonvulsant activity of CF (50-400 mg/kg, p.o .) was assessed using maximal electroshock- (MES), strychnine- (STR) (4 mg/kg, i.p.), picrotoxin- (PTX) (7.5 mg/kg, i.p.), bicuculline- (BIC) (2.7 mg/kg, i.p. ), isoniazid(INH) (250 mg/kg, i.p.) and yohimbine (YHB) (45 mg/kg, s.c. )- induced seizure models in mice. Results: CF (50-400 mg/kg, p.o.) produced significant reduction in the duration of MES-induced seizure with peak effect 20% protection at 200 mg/kg. However, peak effect 60% protection of tonic seizure was obtained at 50 mg/kg following CF pretreatment in strychnine model. Clonazepam (0.5 mg/kg, p.o.) completely abolished picrotoxin-induced seizure while the extract produced 40, 20 and 20% protection, respectively, at 100, 200 and 400 mg/kg. More importantly, CF (100-400 mg/kg) produced 100% inhibition of bicuculline-induced seizure. CF enhanced Gamma amino butyric acid (GABA) activity as observed in significant delay in the onset of tonic/clonic convulsion in isoniazid- and yohimbine-induced seizure, respectively, which was comparable to the effect of clonazepam. Conclusion: The results of study suggest that CF possesses anticonvulsant activity possibly mediated through glycinergic and GABAergic neurotransmission. The results justify the use of the extract in TAM for the treatment of epilepsy and reinforce the value of studying traditional resources as sources of new drug leads.