Extraction-dependent structure–activity relationships of Panax quinquefolius L. polysaccharides: A comparative study

Different extraction methods alter structural features and bioactivities of American ginseng polysaccharides, supporting their high‑efficiency utilization. • Structure‑activity relationships reveal antioxidant, hypoglycemic and hypolipidemic effects depend jointly on monosaccharide composition, molecular weight and spatial conformation. • Comprehensive characterization of higher‑order structures provides theoretical support for targeted modification of polysaccharides in functional food and pharmaceutical fields. This study systematically investigated the structure–activity relationships of six polysaccharide fractions, aiming to elucidate the intrinsic correlations between their structural characteristics and biological activities. The results revealed that the antioxidant, hypoglycemic, and hypolipidemic activities of the polysaccharides were governed not by any single structural factor, but rather by the synergistic effects of monosaccharide composition, molecular weight distribution, and spatial conformation. Among the fractions, ULPP exhibited the most potent broad-spectrum antioxidant and enzyme inhibitory activities through dual chemical and physical mechanisms, suggesting its potential for multi-target intervention. Although DEPP showed weak antioxidant activity, its unique fibrous-lamellar network structure conferred outstanding physical barrier effects and sodium cholate adsorption capacity, indicating distinctive advantages in lipid metabolism regulation. ENPP demonstrated specific inhibitory activity against α-glucosidase, and structural analysis suggested that this activity was closely associated with its specific monosaccharide composition and branching characteristics. In contrast, HWPP and UPPP displayed poor overall activity, likely due to pronounced structural aggregation that limited the exposure of functional groups. These findings lay a theoretical foundation for targeted structural modification of polysaccharides, emphasize the importance of high-order structures in functional assessment, and guide the rational design and development of functional foods.