Abstract: Objective: To observe the effects of sesamin on the abilities of learning and memory in the mice with Alzheimer's disease (AD), and to elucidate their possible mechanisms. Methods: Forty male C57BL/6 mice were randomly divided into control, model, piracetam, low dose of sesamin, and high dose of sesamin groups, and there were 8 mice in each group. The AD models were established by intracerebroventricular injection of amyloid β-protein fragment 25-35 (Aβ_25-35) in the mice in the other groups except control group. 24 h later, the mice in piracetam group were intragastrically administed with piracetam; the mice in low and high doses of sesamin groups were intragastrically administrated of 50 and 100 mg·kg^-1 sesamin, respectively; the mice in control and model groups were intragastrically administrated with the same amount of normal saline once a day for 2 weeks. Morris water maze test was used to observe the escape latencies,the swimming distance and the resident time in target quadrant of the mice in various groups;flow cytometry was used to detect the level of active oxygen(ROS) in brain tissue of the mice in various groups;ELISA was used to detect the activities of superoxide dismutase (SOD) and levels of malondialdehyde (MDA) in brain tissue of the mice in various groups; Western blotting was used to determine the expression levels of apoptosis-related protein B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cysteine aspartate specific proteinase-3 (Caspase-3) proteins in brain tissue of the mice in various groups. Results: Compared with control group,the escape latency of the mice in model group was significantly prolonged (P<0.05), and the swimming distance and the resident time in target quadrant were significantly shortened (P<0.05); compared with model group,the escape latencies of the mice in piracetam group, low dose of sesamin group and high dose of sesamin group were significantly shortened (P<0.05), and the swimming distance and the resident time in target quadrant were significantly increased (P<0.05). Compared with control group, the levels of ROS and MDA in brain tissue of the mice in model group were significantly increased (P<0.05), the SOD activity was significantly decreased (P<0.05), the expression levels of Bax and Caspase-3 protein were significantly increased (P<0.05), and the expression level of Bcl-2 protein and the value of Bcl-2/Bax were significantly decreased (P<0.05); compared with model group, the levels of ROS and MDA in brain tissues of the mice in piracetam, low dose of sesamin, and high dose of sesamin groups were significantly decresed (P<0.05), the activities of SOD were significantly increased (P<0.05), the expression levels of Bax and Caspase-3 proteins were significantly decresed (P<0.05), and the expression levels of Bcl-2 protein and the values of Bcl-2/Bax were significantly increased (P<0.05). Conclusion: Sesamin may improve the learning and memory abilities of the AD model mice by increasing the neuronal antioxidant capacity and inhibiting the neuronal apoptosis.

Key words: sesamin, Alzheimer’s disease, learning and memory, oxidative stress, apoptosis-related proteins