Niosome-Encapsulated Hesperidin Accelerates Antioxidant Defense and TRPM2 Protein Expression to Restore Cognitive Function in a Rat Model of Depression.

AIMS: Hesperidin is a potent antioxidant; however, its therapeutic efficacy is hindered by limited bioavailability. Furthermore, the role of TRPM2 in oxidative stress-induced depression remains to be elucidated. This study investigated the therapeutic potential of niosomal hesperidin in a reserpine-induced depression rat model, focusing on learning and memory performance, oxidative stress markers, and TRPM2 protein expression. METHODS AND MATERIALS: 36 rats were randomly divided into six groups: Control, depression (Reserpine), free hesperidin, Niosomal hesperidin, treatment with hesperidin, and treatment with niosomal hesperidin. Reserpine 0.5mg/kg was administered intraperitoneally for 14 days. Then, rats received hesperidin (20mg/kg, 14 days) and niosomal hesperidin (20mg/kg, 7 days). The novel object recognition and shuttle box tests were performed. Finally, glutathione peroxidase levels, serum superoxide dismutase, and western blotting for TRPM2 protein expression were measured. RESULTS: SOD activity and GPX levels increased in the reserpine-induced rats treated with hesperidin and niosome hesperidin (P<0.05). TRPM2 protein expression decreased in niosome-hesperidin-treated groups compared to the depression group (P<0.0001). The discrimination index increased in the reserpine-induced rats treated with niosome hesperidin compared to the depression group (P<0.001). The total time spent in the white box increased in the shuttle box in the reserpine-induced rats treated with niosome hesperidin compared to the control group (P<0.05). CONCLUSION: Niosomal encapsulation accelerates cognitive recovery and modulates antioxidant capacity and TRPM2 protein expression. Thus, niosomal hesperidin represents a promising nanocarrier strategy for managing depression-related cognitive dysfunction.