Niosome-encapsulated hesperidin accelerates antioxidant defense and TRPM2 protein expression to restore cognitive...

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.

36 rats were randomly divided into six groups: Control, depression (Reserpine), free hesperidin, Niosomal hesperidin, treatment with hesperidin, and treatment with niosomal hesperidin. Reserpine 0.5 mg/kg was administered intraperitoneally for 14 days. Then, rats received hesperidin (20 mg/kg, 14 days) and niosomal hesperidin (20 mg/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.

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).

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.