Polyketides with α-glucosidase inhibitory and neuroprotective activities from Aspergillus versicolor associated with Pedicularis sylvatica

Aspergillus versicolor, an endophytic fungus associated with the herbal medicine Pedicularis sylvatica, produced four new polyketides, aspeversins A-D (1-2 and 5-6) and four known compounds, O-methylaverufin (2), aversin (3), varilactone A (7) and spirosorbicillinol A (8). Their structures were elucidated by extensive spectroscopic data analysis, and their absolute configurations were determined by calculated electronic circular dichroism (ECD) and Mo₂(AcO)₄-induced CD data. Compound 5 was found to exhibit α-glucosidase inhibitory activity with an IC₅₀ value of 25.57 μM. An enzyme kinetic study indicated that 5 was a typical uncompetitive inhibitor toward α-glucosidase, which was supported by a molecular docking study. Moreover, compounds 1-3 and 5 also improved the cell viability of PC12 cells on a 1-methyl-4-phenylpyridinium (MPP⁺)-induced Parkinson's disease model, indicating their neuroprotective potential as antiparkinsonian agents.