Extraction optimization, purification, and structural characterization of Yacon polysaccharide: An inhibitor against α-glucosidase/α-amylase

This study aimed to develop a natural α-glucosidase/α-amylase dual inhibitor from Yacon polysaccharides to address the side effects of clinical synthetic hypoglycemic agents. Using a comprehensive evaluation strategy combining bioactivity and extraction yield, the polysaccharide extraction process was optimized, achieving an 8.26% yield. The most active fraction (YAPa-1) was isolated via bioactivity-guided multi-step column chromatography and its structure was systematically characterized. YAPa-1 exhibited potent dual inhibitory activity: Mixed competitive-uncompetitive inhibition against α-glucosidase (IC₅₀ = 0.0532 mg/mL) and competitive inhibition against α-amylase (IC₅₀ = 0.1158 mg/mL), with efficacy comparable to acarbose. Full characterization of YAPa-1 confirmed it as a 10,873 Da neutral heteropolysaccharide, with defined monosaccharide composition, glycosidic linkages and stable triple-helical conformation. Its complete repeating unit and molecular structure were elucidated, and a sponge-like 3D porous microstructure was revealed.