Evaluation of anti-depressant, anxiolytic, and cognitive improvement effects of nanocurcumin using social isolation model in male mice: Behavioral and histopathological evaluation.

Major Depressive Disorder (MDD) is a heterogeneous mental illness that affects about 10% of people worldwide. Curcumin (Cur) is suggested as a treatment or adjunct treatment of MDD by multiple mechanisms of action. Its effectiveness is limited due to low solubility, poor bioavailability, and rapid metabolization. Different nano-formulations of Cur have been developed to boost its biological activity. The aim of this study was the evaluation of antidepressant/anxiolytic-like effects, and cognitive improvement of nanocurcumin (NCur) in male mice by post-weaning social isolation (PWSI) model to induce depressive/anxiety-like behaviors and cognitive deficits. Mice were housed either in a social group (SG) or an isolated group (IG) for four weeks. After two weeks, IG mice were treated intraperitoneally with NCur (5, 10, 20 mg/kg) and Cur (20 mg/kg) for two weeks. A battery of behavioral tests was used to evaluate depression, anxiety, and cognitive impairment. NCur (20 mg/kg) showed antidepressant-like effect in forced swimming test (P < 0.001) and tail suspension test (P < 0.05), anxiolytic-like effect in elevated plus maze (P < 0.05) and open filed test (P < 0.01), and improved the memory and cognition in passive avoidance test (P < 0.05), but Cur (20 mg/kg) had no effect. Histopathology results showed that NCur (5 mg/kg) led to optimal neuronal survival in CA1, improved cellular organization in CA3, and the highest count of normal neurons in the dentate gyrus. NCur demonstrated potential to treat the depressive/anxiety-like behaviors and impaired cognition induced by the PWSI model in male mice. Histopathological data also showed improvements in hippocampal regions.