Polygonatum sibiricum polysaccharide alleviates type 2 diabetes-associated testicular dysfunction in mice in association with steroidogenesis-related and blood-testis barrier-associated changes

Type 2 diabetes mellitus (T2DM) is closely associated with male reproductive dysfunction, but effective functional food-derived interventions remain limited. Polygonatum sibiricum polysaccharide (PSP), a major bioactive constituent of the medicinal and edible plant Polygonatum sibiricum Redouté, has metabolic regulatory potential. This study evaluated PSP in high-fat diet/streptozotocin (HFD/STZ)-induced T2DM mice. PSP was extracted from geo-authentic Polygonatum sibiricum Redouté collected from the Wudang region of Hubei Province, China, and characterized by SEC-MALLS-RI, HPAEC, and FT-IR. PSP was identified as a high-polysaccharide-content acidic heteropolysaccharide with a broad molecular weight distribution, a weight-average molecular weight of 39.194 kDa and a monosaccharide profile dominated by glucose, galactose, and galacturonic acid. After 5 weeks of oral administration at 400, 800, or 1600 mg kg⁻¹ d⁻¹, PSP altered fasting blood glucose trajectories and tended to improve body weight maintenance. PSP also improved testicular histoarchitecture and sperm quality, accompanied by increased steroidogenesis-related and blood-testis barrier-associated tight junction protein expression. Group-level sperm malformation decreased from 49.3% in model mice to 35.8% and 25.4% in the medium- and high-dose groups, respectively. PSP treatment was associated with reduced ROS-associated fluorescence, attenuated NF-κB-related signaling, and lower Tnf, Il1b, and Il6 mRNA expression. Overall, PSP may alleviate T2DM-associated testicular dysfunction in association with improved systemic metabolic status and favorable changes in the local testicular microenvironment. These findings support PSP as a potential multi-target functional food-derived candidate for diabetes-associated male reproductive injury, although further studies are required to clarify its direct targets and causal mechanisms.