Selenization-based nanotechnology improves the hypoglycemic and anti-osteoporotic efficacy of Rehmannia glutinosa polysaccharide.

The global prevalence of type 2 diabetes mellitus (T2DM) continues to rise, with diabetic osteoporosis (T2DOP) representing a common yet insufficiently addressed complication. In this study, we synthesized selenium-Rehmannia glutinosa polysaccharide nanoparticles (Se-RGP NPs) characterized by an average particle size of 91.35 nm, a polydispersity index (PDI) of 0.231, and a spherical morphology. The Se-RGP NPs exhibited excellent stability during storage and in physiological media, displaying greater inhibitory activity against α-amylase and α-glucosidase than free RGP. Compared with free RGP, Se-RGP NPs demonstrated significantly enhanced cellular uptake, improved capacity to scavenge intracellular reactive oxygen species (ROS), stabilized mitochondrial membrane potential (MMP), and restored mitochondrial function in insulin-resistant (IR) cell models, along with markedly increased oral bioavailability. In streptozotocin (STZ)-induced T2DM mice complicated with osteoporosis, administration of 10 mg/kg of Se-RGP NPs achieved a hypoglycemic efficacy equivalent to that of 80 mg/kg of free RGP. At doses of 20 and 30 mg/kg, Se-RGP NPs further reduced blood glucose levels, repaired pancreatic islets, improved blood lipid profiles, and ameliorated bone microstructure. No significant side effects were observed during treatment with Se-RGP NPs. The improved therapeutic efficacy of RGP was attributed to both improved oral absorption facilitated by nanotechnology and the synergistic actions of selenium. Selenization of nanoparticles offers a novel strategy to enhance the therapeutic potential of bioactive polysaccharides such as RGP in managing diseases associated with excessive ROS activation.