Abstract: Objective: To study the anti-aging effect of Agaricus blazei polyssaccharide-A (ABP-A) in the aging model mice induced by D-galactose (D-Gal), and to explore the anti-aging mechanism of Agaricus blazei polysaccharide(ABP). Methods: The crude polysaccharide from Agaricus blazei Murill(ABM) was extracted by water extraction and alcohol precipitation, and the fractions were analyzed by DEAE-cellulose ion exchange column chromatography;ABP-Awas obtained.A total of 48 male ICR mice were randomly divided into control group, model group, positive drug group(Piracetam)and ABP-A group(n=12). Morris water maze, dark avoidance and platform jumping behavior experiments were performed at 70 d after administration. The superoxide dismutase (SOD) activitives, the malondialdehyde (MDA) levels,the total antioxidant capacities (T-AOC), the catalase (CAT) activitives, and the reactive oxygen species (ROS) levels in serum of the mice in various groups were detected. Western blotting method was used to detect the expression levels of Nrf2, Keap1 and HO-1 proteins in the brain tissue of the mice in various groups. Results: The total sugar content of ABP was 75.1%. The ABP-A was graded and gained by DEAE-cellulose ion exchange column chromatography.The behavioral experiment results showed that compared with model group, the dark avoidance latency of the mice in ABP-A group was significantly lengthened (P<0.05), the number of errors was decreased significantly (P<0.05); the latency of step down was significantly prolonged (P<0.05), and the number of errors was decreased significantly (P<0.05); the positioning latency of the mice in ABP-A group was significantly shortened(P<0.05), and the number of entering to the platform was increased significantly (P<0.05). Compared with model group, the activities of serum SOD and CAT of the mice in ABP-A group were increased(P<0.05),the T-AOC was increased(P<0.05), the levels of MDA and ROS were decreased(P<0.05).The Western blotting results showed that compared with model group, the expression level of HO-1 protein in the brain tissue of the mice in ABP-A group was increased (P<0.05), and the expression levels of Nrf2 and Keap1 proteins were decreased (P<0.05 or P<0.01). Conclusion: ABP can improve the learning and memory ability of the aging model mice, and its mechanism may be related to regulating Keap1/Nrf2/ARE oxidative stress pathway related factors Nrf2, Keap1, and HO-1 with Nrf2 as the core to perform the anti-aging effect.

Key words: Agaricus blazei polysaccharide, anti-aging, learning and memory ability, Keap1/Nrf2/ARE signal pathway