Processing-induced structural remodeling enhances the hypoglycemic activity of Polygonatum cyrtonema Hua polysaccharides via gut microbiota-SCFA-GPR41/43 pathway.

Type 2 diabetes mellitus (T2DM) poses a major health and socioeconomic challenge, and long-term use of conventional hypoglycemic agents often causes adverse effects such as impaired gastrointestinal function. Natural polysaccharides have emerged as promising alternatives due to their safety and bioactivity. In this study, polysaccharides from raw Polygonatum cyrtonema Hua (RPCP) and processed Polygonatum cyrtonema Hua (PPCP) were successfully extracted using enzyme-assisted hot water extraction. The purified fractions of RPCP (RPCP-P) and PPCP (PPCP-P) were structurally characterized by molecular weight determination, monosaccharide composition, FT-IR, methylation, and NMR analyses. Their hypoglycemic effects and underlying mechanisms were evaluated in high-fat diet and streptozotocin-induced T2DM mice. Both RPCP and PPCP significantly reduced fasting blood glucose, improved insulin sensitivity, and ameliorated lipid metabolism disorders. Mechanistically, the polysaccharides modulated gut microbiota composition, promoted short-chain fatty acid (SCFA) production, upregulated colonic GPR41/43 expression, and increased glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretion, thereby improving glucose homeostasis. Notably, PPCP exhibited superior antidiabetic effects to those of RPCP, which we attribute to its greater molecular heterogeneity and galactan-rich structure, suggesting that traditional steaming enhances polysaccharide bioactivity. These findings demonstrate that traditional processing enhances the functionality of Polygonatum cyrtonema polysaccharides through structure-dependent modulation of the gut microbiota-SCFA-host metabolic axis, providing a scientific basis for their development as functional food ingredients for glycemic regulation.