Structural characterization and mechanisms of anti-diabetic activity of a novel polysaccharide with a fructose backbone from Polygonatum cyrtonema Hua

In this study, a novel homogeneous polysaccharide (PCP-J-1, 7.384 kDa) with a fructose backbone was isolated from the roots of Polygonatum cyrtonema Hua (PCH). Structural analysis revealed that its main chain consists of →1)-β-D-fructofuranosyl-(2 → and →1,6)-β-D-fructofuranosyl-(2 → residues, with side chains of β-D-fructofuranosyl-(2 → attached to the O-6 position of →1,6)-β-D-fructofuranosyl-(2→. Oral administration of PCP-J-1 to mice with type 2 diabetes mellitus (T2DM) reduced fasting blood glucose (FBG) by 33.2% in the high-dose group compared with the model group, and decreased glycosylated hemoglobin (GHbA1c) levels by 19.7% in the high-dose group. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was reduced by 42.9% whereas serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were lowered by 30.3%, 34.8%, and 37.0%, and high-density lipoprotein cholesterol (HDLC) was elevated by 39.2% in the high-dose group. PCP-J-1 treatment improved oral glucose tolerance, reducing the area under the curve (AUC) by 17.0% in the high-dose group, and also ameliorated liver pathology and intestinal barrier integrity. Mechanistically, the treatment was associated with an increased abundance of beneficial gut bacteria (such as Faecalibaculum) and elevated production of short-chain fatty acids (SCFAs). These changes correlated with upregulated colonic FFAR2/FFAR3 expression and increased plasma glucagon-like peptide-1 (GLP-1) levels. Together, these effects alleviated T2DM symptoms in mice. Collectively, our findings provide a structural and mechanistic basis for the development of PCH polysaccharides as functional foods or therapeutic agents for T2DM.