Mechanism of Anticonvulsant Effects of Ethanol Leaf Extract and Fractions of Milicia excelsa (Moraceae) in Mice

Abstract

Aims: This study investigated the anticonvulsant potential of ethanol leaf extract and fractions of Milicia excelsa (Moraceae). Study Design: This study used experimental animal models predictive of human convulsion in mice. Place and Duration of Study: Department of Pharmacology, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria, between January 2014 and  February 2015. Methodology: The anticonvulsant effect of ethanol leaf extract (EME), n-hexane (HF), ethyl acetate (EAF), n-butanol (BF) and aqueous (AF) fractions of the extract was evaluated using picrotoxin-, pentylenetetrazole-, and strychnine-induced convulsion models. The neural mechanism of anticonvulsant effect of the most active fraction (AF) was also investigated using flumazenil (3 mg/kg, i.p.), cyproheptadine (4 mg/kg, i.p.) and L-NG-Nitroarginine (10 mg/kg, i.p.) in picrotoxin-induced convulsion model. Results: EME and AF significantly (P < .05) delayed the onset of clonic and tonic convulsions and prolonged death latency with varying degrees of protection in picrotoxin-, and pentylenetetrazole-induced convulsion models. EME, EAF and AF significantly (P < .05) pronlonged the onset of clonic convulsion in strychnine-induced convulsion in mice. Flumazenil, cyproheptadine and L-NG-Nitroarginine abolished the anticonvulsant effect of AF suggesting the involvement of GABAergic, serotonergic and nitergic pathways. Conclusion: This study concludes that Milicia excelsa leaf contains biologically active anticonvulsant principles, thus lending pharmacological credence to the suggested traditional use. Further study may be undertaken to isolate and elucidate the chemical structure of the biologically active ingredient(s) responsible for the observed anticonvulsant effect.