Lion’s mane mushroom has long been prized in both cuisine and traditional medicine, but its glycoproteins, molecules in which protein chains are covalently linked to sugar moieties, have remained largely unexplored territory. The research team set out to fill that gap by isolating a glycoprotein they designated HEP from the fruiting body and subjecting it to a battery of structural analyses. Sodium dodecyl sulfate polyacrylamide gel electrophoresis, or SDS-PAGE, was used to resolve the protein components by molecular weight, while periodic acid-Schiff staining confirmed the presence of carbohydrate groups attached to the protein backbone.

To probe the molecule’s chemical architecture further, the researchers turned to Fourier-transform infrared spectroscopy, a technique that reveals characteristic absorption bands corresponding to peptide bonds, glycosidic linkages, and other functional groups. Liquid chromatography coupled with tandem mass spectrometry, or LC-MS/MS, then allowed the team to identify the amino acid sequences and glycan features of the purified compound. Together, these methods showed that HEP adopts a secondary structure dominated by alpha-helices, interspersed with random coil regions, a conformational profile that may be relevant to how the molecule interacts with biological targets in the gut and liver.

With the structure characterized, the team moved to an animal model of type 2 diabetes that closely mimics the human disease trajectory. Twenty-five male ICR mice were assigned to five groups: a healthy control group, a diabetes model group, a positive control group treated with the standard drug metformin, and two groups receiving HEP at low and high doses. Diabetes was induced by feeding the animals a high-fat diet followed by injection with streptozotocin, a chemical that damages insulin-producing pancreatic beta cells and produces hyperglycemia characteristic of the disease.

After one week of streptozotocin injections established the diabetic state, HEP was administered orally for two consecutive weeks as part of a five-week dietary intervention period. The results were notable. Mice receiving the glycoprotein showed significantly reduced fasting blood glucose compared with untreated diabetic animals. Their response to insulin improved, as did their ability to clear glucose from the bloodstream during tolerance tests, two measures that reflect the core defects of type 2 diabetes: insulin resistance and impaired glucose disposal.

Beyond glycemic control, HEP treatment alleviated two of the most troublesome complications of the disease. Dyslipidemia, the abnormal elevation of circulating fats that raises cardiovascular risk, was reduced in the treated animals. Hepatic steatosis, the accumulation of fat droplets in liver tissue that can progress to inflammation and fibrosis, was also visibly and measurably eased. These systemic improvements suggest that the glycoprotein acts on multiple metabolic pathways rather than a single target.

To understand the mechanism, the researchers examined the hepatic PI3K/AKT signaling pathway, a cascade central to how insulin instructs cells to take up glucose and store it properly. In type 2 diabetes, this pathway becomes blunted, contributing to persistent high blood sugar. HEP treatment was associated with reactivation of this pathway, indicating that the glycoprotein helps restore insulin signaling in the liver. At the same time, markers of oxidative stress, which arises when reactive oxygen species overwhelm cellular antioxidant defenses and damage tissues, were reduced following treatment.

Inflammation also receded. Pro-inflammatory cytokines, signaling molecules that drive chronic low-grade inflammation in obese and diabetic tissue, were downregulated in mice receiving HEP. This anti-inflammatory effect is significant because inflammation is now understood to be both a consequence and a driver of insulin resistance, creating a vicious cycle that the glycoprotein appears to interrupt.

Perhaps the most intriguing findings emerged from the gut. Sequencing of microbial communities revealed that HEP reshaped the composition of the gut microbiota, the trillions of bacteria that inhabit the intestine and profoundly influence host metabolism. Type 2 diabetes is associated with characteristic disruptions in microbial diversity and function, and HEP treatment reversed many of these disturbances. The researchers also profiled metabolites, the small molecules produced by microbial and host metabolism, and found that key metabolites correlated with diabetic parameters, suggesting a link between microbial changes and the observed metabolic improvements.

The study, led by corresponding authors Peng Liu and Yan Yang with co-first authors Ximei Wang and Yuanfeng Wang, was supported by the National Key Research and Development Program of China, the Shanghai Natural Science Foundation, and the Shanghai Leading Talent Program. The authors state no competing interests. While the results are limited to a mouse model and two weeks of treatment, they position Hericium erinaceus glycoproteins as promising natural nutraceutical candidates for managing type 2 diabetes, and they underscore how advanced structural and multi-omics approaches are transforming our understanding of food-derived bioactive molecules.

Subject of Research: A glycoprotein from Hericium erinaceus that attenuates metabolic disorders in type 2 diabetic mice

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

Article References: Wang, X., Wang, Y., Wu, D., Chen, W., Li, W., Zhang, Z., Li, Z., Zhu, J., Liu, J., Liu, P., & Yang, Y. (2026). A glycoprotein from Hericium erinaceus attenuates metabolic disorders in type 2 diabetic mice. npj Science of Food. https://doi.org/10.1038/s41538-026-01205-8

Image Credits: AI Generated

DOI: 10.1038/s41538-026-01205-8

Keywords: Hericium erinaceus, glycoprotein, type 2 diabetes, gut microbiota, PI3K/AKT signaling, hepatic steatosis, insulin resistance, oxidative stress, nutraceutical, metabolomics, edible fungi, mouse model