Antidepressant and anxiolytic activities of Cochlospermum religiosum leaf extract, synergism with antidepressants, and molecular docking studies

Abstract

The leaves of Cochlospermum religiosum were investigated for the antidepressant and anxiolytic activities in mice using behavioural models like spontaneous locomotor activity, forced swim test, tail suspension test, elevated plus maze and marble burying behaviour. The mechanism was studied using Reserpine-induced hypothermia (RIH) model and in silico molecular docking. The leaf extract exhibited significant antidepressant and anxiolytic effects (P <0.05 for 50 mg/kgb.w.,p.o./P <0.01 for 100 mg/kgb.w., p.o.) in mice without an impact on baseline locomotor activity. The result from Reserpine-induced hypothermia rat model revealed that the leaf extract (50 mg/kgb.w., p.o.) significantly antagonized the effect (P <0.05) of Reserpine. Furthermore, synergistic effect was evaluated by coadministration of the leaf extracts with fluoxetine (10 mg/kg, i.p.) and imipramine (10 mg/kg, i.p.) at sub-therapeutic dose levels. Synergistic effect of the leaf extract was significant (P <0.05) for both antidepressant and anxiolytic activities as compared to therapeutic doses of extract, imipramine, and fluoxetine. The molecular docking studies for the chemical constituents of the leaves on 5HT1B, 5HT2A, β1 and β2 crystal structures revealed that pentagalloyl glucose showed typical binding with higher affinity on 5HT1B (-10.79) and 5HT2A(-10.33) than fluoxetine and imipramine. Cynarine docked on β-2 receptor with score of -13.582 at binding site of timolol, and similarly, it binds with 5HT1B and 5HT2A at serotonin binding site.