Polysaccharides from Acanthopanax senticosus (Rupr. et Maxim.) Harms: Molecular Messengers Linking the Traditional Efficacy of Fortifying the Spleen, Replenishing Qi, and Calming the Spirit to Gut-Immune Axis Regulation

• ASPS bridges TCM efficacy with gut-immune-brain axes • A structure-activity relationship framework for ASPS is outlined • Mechanisms involve barrier repair, microbiota remodeling, and SCFAs • Bidirectional immunomodulation underpins the replenishing Qi effect • Translational challenges and future directions are proposed Acanthopanax senticosus (Rupr. et Maxim.) Harms , a fundamental botanical in Traditional Chinese Medicine (TCM), is prescribed to fortify the spleen, replenish Qi, and calm the spirit. Its polysaccharide constituents, designated A. senticosus polysaccharides (ASPS), have emerged as a prominent research focus due to their broad-target bioactivity and favorable safety profile. This review systematically analyzes the structure-activity relationships of ASPS and elucidates the mechanisms by which they mediate traditional therapeutic effects, primarily via signaling along the gut-immune and gut-brain axes. Evidence indicates that ASPS fortify the spleen by enhancing intestinal barrier integrity, modulating gut microbiota composition, and promoting the production of short-chain fatty acids (SCFAs). They replenish Qi via bidirectional immunomodulation and calm the spirit through gut-brain axis-mediated mechanisms, including antioxidant, anti-neuroinflammatory, and anti-apoptotic activities. The review also addresses challenges in ASPS development, including raw material standardization, enhancement of oral bioavailability, and elucidation of structure-function mechanisms, while exploring its potential applications in functional foods and adjunctive therapies.