Antidepressant-like effect of Entada Africana Guill. & Perr. (Fabaceae) in mice: Involvement of monoamine neurotransmitters, cortisol, BDNF, and oxidative stress

• EEEA produced a significant antidepressant-like effect in the chronic model of depression. • The antidepressant activity of EEEA may likely involve the adrenergic, serotonergic, and dopaminergic monoamine neurotransmitter systems. • Cortisol, BDNF, and oxidative stress biomarkers have been implicated in the antidepressant-like effect of EEEA. • The activity of EEEA might be due to the presence of flavonoids, saponins, terpenoids, and tannins. Entada africana is used to treat various disease conditions including stomach ache, cataract, liver disease, epilepsy and depression. Previous research reported its antidepressant properties in acute depression models. However, its activity in chronic model and the associated signaling pathways remain unclear. To elucidate the antidepressant-like effect of ethanol leaf extract of Entada africana (EEEA) in chronic model of depression and the possible mechanism(s). Limit test was utilized in determining the oral median lethal dose (LD 50 ). To establish the potential roles of monoamine neurotransmitters in the antidepressant action of EEEA, groups of mice were pre-administered prazosin (1 mg/kg), cyproheptadine (3 mg/kg), and haloperidol (0.2 mg/kg), 30 minutes before administering EEEA (4 mg/kg) or imipramine (10 mg/kg). In a separate experiment, animals were depressed via chronic unpredictable mild stress (CUMS), followed by sucrose preference, open field (OF), and tail suspension (TS) tests. The quantities of cortisol, brain-derived neurotrophic factor (BDNF), superoxide dismutase, and malondialdehyde were estimated. Phytochemical profiling of the extract was also conducted. The oral LD 50 was estimated to be > 2000 mg/kg in mice. Pre-administration of prazosin, cyproheptadine, and haloperidol significantly (p < 0.05) attenuated the antidepressant action of EEEA. In CUMS experiment, EEEA remarkably (p < 0.05) reversed the weight loss, improved sucrose consumption, increased exploration in OF, and shortened the duration of motionlessness. EEEA significantly (p < 0.05) lowered the serum cortisol, increased BDNF concentration, and ameliorated oxidative stress. Flavonoids, saponins, terpenoids and tannins were identified. Entada africana exerted antidepressant-like effect in chronic model of depression, which may be mediated via modifications of monoamine NTs, cortisol, BDNF, and oxidative stress pathways.