Background: In view of the increasing human life and the aging of the population, the search for safe anti-aging drugs has become a hot topic. Agaricus blazei Murrill is a rare edible fungus, with a variety of biological activities. The purpose of this study was to clarify the anti-aging effect and mechanism of ABM-A on the aging induced by D-Galactose in mice.

Results: The result showed that ABM-A contained 87.2% of glucose, 3.3% of galactose, 3.8% mannose and 5.7% gluconic acid. The behavior of mice in the treatment group was significantly improved after administration of ABM-A. And the activity of SOD and CAT and the level of T-AOC were increased (p < 0.05), the content of MDA and ROS was decreased (p < 0.05) in the serum of mice in ABM-A group. The results of mechanism research showed that nine genes were screened out by functional annotation and enrichment analysis for the verification by RT-qPCR, and the results of RT-qPCR were consistent with those of RNA-seq. Western Blot results showed that ABM-A upregulated the expression of Hmox1, Myd88, p-c-Jun, Apc, Bmil, Cox7a2l and Ndufv1, down-regulated the expression of Nfe2l2, Keap1, Apoe, Mapk1and Atp1a3, and decreased the phosphorylation of p38 and Jnk, suggesting that it may play an anti-aging effect by regulating Nrf2/ARE and MAPKs superfamily signal pathways.

Conclusions: ABM-A can reduce oxidation reaction and play an anti-aging role through Keap1-Nrf2/ARE and MAPKs signaling pathway.