Anti-inflammatory potential of Astragalus polysaccharides: structural characteristics, mechanisms and clinical translation

Astragalus polysaccharides (APS) are important bioactive macromolecules derived from Astragalus mongholicus Bunge, with potential anti-inflammatory properties. However, APS are structurally complex and highly heterogeneous natural polysaccharides and their structural characteristics, such as molecular weight, monosaccharide composition, glycosidic linkage types, and branching patterns, may all affect their biological activities. In addition, factors such as plant source, medicinal part, extraction and processing methods, degradation, and structural modifications can further contribute to structural differences among various APS preparations. Due to the complexity of the fine structure of polysaccharides and the limitations of current methods for structural characterization and functional validation, the relationship between the specific structural features of APS and their anti-inflammatory activity has not yet been fully elucidated. In recent years, research into the anti-inflammatory mechanisms of APS has continued to deepen, encompassing multiple regulatory levels such as inflammatory signaling, oxidative stress, cellular homeostasis, macrophage function, and the gut microbiota. Based on this, this review focuses on the potential links between the structural characteristics of APS and their anti-inflammatory activity, and comprehensively summarizes the anti-inflammatory mechanisms of APS and research progress in inflammation-related diseases. At the same time, given the significant variations in experimental design and the depth of validation among existing structure-activity relationship studies, this review conducts a tiered evaluation of relevant structure-activity relationships and anti-inflammatory mechanisms based on specific APS preparations, taking into account the directness of evidence provided by different types of studies. By comparing the results of various studies, this review aims to further clarify the structural basis of the anti-inflammatory effect of APS and provide a reference for further research and development. Furthermore, this review discusses the pharmacokinetic characteristics of APS, novel delivery strategies, and the major challenges facing clinical translation.