Antihyperglycemic nor-chamigrane sesquiterpenoids from the fungus Antrodiella albocinnanmomea.

Eight previously undescribed nor-chamigrane sesquiterpenoids, designated as antrodiellones A‒H (1‒8), were isolated from fermentation broth of Antrodiella albocinnamomea. Notably, antrodiellone A (1) features a unique carbon skeleton. Their structures were elucidated by comprehensive spectroscopic analyses, quantum calculations, and X-ray crystallography. Antihyperglycemic evaluation revealed that all compounds, as well as the positive control metformin, dose-dependently enhanced glucose consumption in insulin-resistant (IR) HepG2 cells. Specifically, compounds 1 and 3 upregulated the mRNA expression of serine/threonine kinase (AKT) and glucose transporter type 4 (GLUT4) genes, while downregulating phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Furthermore, these compounds significantly increased GLUT4 protein expression. These findings suggest that these nor-sesquiterpenoids may hold therapeutic potential for managing metabolic disorders associated with insulin resistance.