Antidepressant and anxiolytic effects of amentoflavone isolated from Cnestis ferruginea in mice

The root decoction of Cnestis ferruginea (CF) Vahl DC (Connaraceae) is used in traditional African medicine in the management of psychiatric disorders. This study presents the antidepressant and anxiolytic effects of amentoflavone (CF-2) isolated from the root extract of C. ferruginea. The antidepressant effect was studied using the forced swimming (FST) and tail suspension tests (TST) while the hole-board, elevated plus maze (EPM) and light/dark tests were used to evaluate the anxiolytic effect. Acute treatment with CF extract and amentofiavone significantly (p<0.001) reduced the duration of immobility in FST and TST with peak effects observed at 100 and 50 mg/kg respectively in comparison to control treated. Antidepressant effects of CF and amentoflavone were significantly higher (p<0.05) when compared to imipramine in FST but comparable to the fluoxetine treated group in TST. The pretreatment of mice with metergoline (4 mg/kg, i.p., a 5-HT2 receptor antagonist), prazosin (62.5 mu g/kg, i.p., an alpha 1-adrenoceptor antagonist), and yohimbine (1 mg/kg, i.p., an alpha 2-adrenoceptor antagonist), but not sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist), cyproheptadine (3 mg/kg, i.p., a 5-HT2 receptor antagonist), atropine (1 mg/kg, i.p., a muscarinic receptor antagonist) 15 mins before the administration of amentoflavone (50 mg/kg; p.o.) significantly prevented its antiimmobility effect in the FST. CF extract and CF-2 significantly (p<0.05) attenuated anxiety by increasing the number of head-dips in the hole-board test, the time spent on the open arms in the EPM, and the exploration of the light chamber in the light/dark test. Pretreatment with flumazenil (3 mg/kg, i.p., ionotropic GABA receptor antagonist) 15 min before oral administration of amentoflavone (25 mg/kg) significantly reduced the time spent in the open arms in EPM. It is concluded from the results obtained that amentoflavone produces its antidepressant effect through interaction with 5-HT2 receptor and alpha 1-, and alpha 2-adrenoceptors while the anxiolytic effect involved the ionotropic GABA receptor. (C) 2012 Published by Elsevier Inc.