A glycoprotein from Hericium erinaceus attenuates metabolic disorders in type 2 diabetic mice

Hericium erinaceus is a well‑known edible and medicinal mushroom, yet its glycoproteins remain largely unexplored. In this study, a glycoprotein (HEP) was isolated from H. erinaceus and characterized by SDS–PAGE, PAS staining, FT–IR, and LC–MS/MS. Structural analysis revealed that HEP exhibits an α‑helix‑rich conformation with random coils and characteristic. The hypoglycemic effects of HEP were evaluated in a high‑fat diet combined with streptozotocin‑induced type 2 diabetes mellitus (T2DM) mouse model. Twenty‑five male ICR mice were randomly divided into control, T2DM model, metformin positive control, and HEP low‑dose and high‑dose groups. After five weeks of dietary intervention and 1 week of streptozocin injection, HEP was administered orally for two consecutive weeks. HEP treatment significantly reduced fasting blood glucose, improved insulin sensitivity and glucose tolerance, and alleviated dyslipidemia and hepatic steatosis. HEP was associated with reactivation of the hepatic PI3K/AKT signaling pathway, reduction of oxidative stress, and downregulation of pro‑inflammatory cytokines. Additionally, HEP reshaped the gut microbiota composition and reversed T2DM‑associated metabolic disturbances, with key metabolites correlated with diabetic parameters. This study highlights the potential of H. erinaceus as a natural nutraceutical candidates for managing T2DM.