AUTHOR=Wang Bo , Wu Banglong , Ma Yingjuan , Liu Xiaofeng , Tao Lijun , Jia Limin , Ding Xiaoling , Zhou Xuebing 

TITLE=Astragalus polysaccharides: structure-immunomodulation relationships, multi-target pharmacological activities, and cutting-edge applications in immune modulation

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1714898

DOI=10.3389/fimmu.2025.1714898

ISSN=1664-3224

ABSTRACT=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.