Bo Wang, Bing Wu, Yaohong Ma, Xiaofeng Liu, Lijun Tao, Lin Jia, Xiaoling Ding, Xuebing Zhou
Astragalus Polysaccharide (APS), the primary bioactive component of Astragalus, exhibits multi-faceted immunomodulatory properties. Its efficacy stems not from broad, non-specific stimulation but from the precise engagement of a network of cell surface immune receptors. This review synthesizes the critical structure-immunomodulatory network relationship of APS, positioning Toll-like receptor 4 as a central mediator. Key insights reveal that APS bioactivity is governed by a specific molecular weight window, critical monosaccharide ratios, and distinct glycosidic linkages. These structural features enable APS to interact with TLR4, potentially in collaboration with other pattern recognition receptors such as the Mannose Receptor and Dectin-1, to initiate integrated signaling. Future research must prioritize multi-omics and structural biology to map precise receptor-binding sites, establish robust standardization and quality control protocols, and advance translational clinical studies for APS-based adjuvant development. This work provides a strategic framework for advancing APS from a traditional remedy into a novel, mechanism-driven immunomodulatory agent.