Effect of cyclodextrin-complexed lyophilized nanosuspension of Nigella sativa seeds oleoresin on chronic unpredictable mild stress (CUMS)-induced depression in mice

Depression is a prevalent global health concern necessitating alternative approaches to conventional antide­
pressant medications due to its associated adverse effects. Nigella sativa (NS) is recognized for its potential as an
antidepressant, offering a promising solution with fewer side effects. This study investigated the antidepressant
efficacy of cyclodextrin-complexed lyophilized nanosuspension of NS oleoresin (NSOR) in a murine model of
chronic unpredictable mild stress (CUMS)-induced depression. This study sought to evaluate and contrast the
antidepressant potential of the nano-NSOR with that of the NS ethanolic extract (NSEE). The prepared nano-NSOR was characterized physicochemically and evaluated for in vitro drug release and in vivo antidepressant activity. The particle size of nano-NSOR was determined to be 164.6 nm. In vitro drug release studies suggested the higher drug release from nano-NSOR (90.15 % after 72 h) compared to the native NSOR (59.55 % after 72 h). Furthermore, nano-NSOR exhibited a more pronounced antidepressant effect than NSEE in the context of CUMS-induced depression. This study highlights a potential alternative for managing depression, addressing the need for improved antidepressant treatments with reduced side effects. These results suggest that nano-NSOR ame­
liorates CUMS-induced depression by modulating neurotransmitter levels, reducing inflammation, and
enhancing neuroprotection.