Optimization of Morchella sextelata polysaccharide-stabilized selenium nanoparticles and evaluation of their hypoglycemic activity in vitro and in vivo

Natural polysaccharides have been widely used in the synthesis of functional selenium nanoparticles (SeNPs) in recent years. In this study, Morchella sextelata polysaccharide (MSP), a newly identified fungal polysaccharide, was employed as a biocompatible stabilizer for the SeNPs synthesis. The preparation of MSP4-SeNPs was systematically optimized by single-factor screening and response-surface methodology. By establishing an insulin-resistant HepG2 cell model, we demonstrated that MSP4-SeNPs effectively ameliorate insulin resistance in IR-HepG2 cells. The results showed that MSP4-SeNPs alleviated oxidative stress by elevating the activities of hexokinase (HK) and pyruvate kinase (PK) activities, promoting hepatic glycogen synthesis, and enhancing the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), while concurrently reducing malondialdehyde (MDA) and triglyceride (TG) levels. Acute-toxicity assays in mice revealed that MSP4-SeNPs exhibited a favorable safety profile, with the safe dosage range of 0–4 mg/kg. By employing a type 2 diabetic mouse model, we found that MSP4-SeNPs intervention significantly normalized the perturbed serum biochemical signature, as evidenced by lowered blood glucose levels, improved lipid profiles, and restored hepatic enzyme activities. Histopathological analysis demonstrated that MSP4-SeNPs markedly alleviate diabetes-induced morphological lesions in liver, kidney, and pancreas, suggesting their broad organ-protective effects. These results demonstrated that MSP4-SeNPs exhibited promising therapeutic potential for type 2 diabetes by alleviating oxidative stress and regulating key enzymes in glucose metabolism. • The preparation process of MSP4-SeNPs was optimized through single-factor experiments and response surface methodology. • MSP4-SeNPs ameliorate diabetic metabolic dysfunction via improved glycogenesis and reduced hepatorenal oxidative stress. • MSP4-SeNPs alleviate diabetes-induced tissue damage in liver, kidney, and pancreas.