Abstract: This study characterized Anemarrhena asphodeloides Bge. polysaccharides (AABP) and evaluated their protective effects against D-galactose (D-gal)-induced brain injury and gut microbiota dysbiosis in aging mice. The results indicated that AABP, with a purity of 80.89%, were primarily composed of mannose and glucose, featured a triple-helix structure and possessed significant in vitro antioxidant capacity. AABP significantly improved the behavioral performance of aging mice and alleviated neuronal pathological damage in the hippocampus. Mechanistically, AABP effectively enhanced the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) while reducing malondialdehyde (MDA) levels in brain tissue. Moreover, they activated the downstream protein kinase B (Akt)/cAMP-response element binding protein (CREB) signaling pathway by upregulating brain-derived neurotrophic factor (BDNF) expression. Furthermore, 16S rRNA sequencing and functional prediction using PICRUSt2 revealed that AABP restored the α-diversity of the gut microbiota and the relative abundance of key genera, such as Lachnospiraceae_NK4A136_group and Alloprevotella, while enhancing carbohydrate and amino acid metabolism. In summary, AABP may exert anti-aging effects by activating the cerebral BDNF/Akt/CREB signaling pathway and remodeling gut microbiota homeostasis.

Key words: Anemarrhena asphodeloides Bge. polysaccharides; structural characterization; aging mice; brain-derived neurotrophic factor; protein kinase B/cAMP-response element binding protein signaling pathway; gut microbiota