Antidepressant-Like Effect of an Immediate-Release Formulation of Mallotus oppositifolius in Mice

Background: Antidepressant-like effects of the crude extract of Mallotus oppositifolius (MOE) have been previously demonstrated. However, to overcome the limitations of crude extracts as medicines, we produced an immediate-release formulation of MOE (MOE-IR) and tested its efficacy. Methods: Using the wet granulation method, MOE was formulated into immediate-release dosage forms (MOE-IR F₁ and F₂, 10, 30, 100 mg) and flow properties were assessed with bulk density, tapped density, Carr’s index, Hausner’s ratio, and the angle of repose. In vitro dissolution and antioxidant studies were conducted. Murine unpredictable chronic mild stress and sucrose preference tests (UCMS-SPTs) assessed the antidepressant-like effect. Except for the vehicle nonstressed (VEH-NS) group, mice were subjected to the UCMS for 7 weeks while receiving normal saline (VEH-S, 10 mL/kg; p.o.), MOE-IR (10, 30, and 100 mg/kg; p.o.), or fluoxetine (FLX 20 mg/kg; p.o.) daily for 5 weeks. The weight of mice and sucrose consumption (test for anhedonia) were monitored, after which forced swim test (FST), tail suspension test (TST), and open field test (OFT) were conducted following treatment termination. Plasma corticosterone concentration was assessed using ELISA, and brains were harvested for Golgi-Cox staining. Results: MOE-IR F₁ (10 mg) exhibited the most suitable formulation properties, and the highest release profile in all media, hence, was selected for the proof-of-concept antidepressant study and referred to as MOE-IR. MOE-IR and crude extract demonstrated in vitro antioxidant activity in the DPPH test. MOE-IR just as FLX reversed the stress-induced weight loss, anhedonia as well as decreased immobility time in the FST and TST without affecting locomotor activity. MOE-IR decreased the plasma corticosterone concentration and increased the dentate gyrus (DG) dendritic spine density. Conclusion: Collectively, MOE-IR demonstrated antidepressant-like that may be associated with antioxidant effects, decreased plasma corticosterone levels, and increased DG dendritic spine density.