Multi-target anti-diabetic styrylpyrones from Phellinus igniarius: Inhibition of α-glucosidase, protein glycation, and oxidative stress

Bioactivity screening revealed that the EtOAc extract from the culture broth of Phellinus igniarius SY489 exhibited remarkable α -glucosidase inhibitory activity, with an IC 50 value of 1.92 μg/mL. Activity- and ultraviolet (UV) profile-guided isolation led to the discovery of four anti-diabetic styrylpyrones ( 1 – 4 ), including two novel compounds, phelignidins A ( 1 ) and B ( 2 ). Compounds 1 and 2 represent a rare structural type of styrylpyrone dimer, in which one of the pyrone moieties exists in an open-ring state. The absolute configurations of the new compounds 1 and 2 , as well as the previously unresolved compound 3 , were established. Compounds 1 – 4 were effective in α -glucosidase inhibition, anti-glycation, and antioxidant assays, surpassing or being comparable to the positive control drugs, with minimal cytotoxicity. Furthermore, studies on α -glucosidase inhibition mechanisms suggested that these compounds interact with α -glucosidase at a single binding site, causing secondary structure unfolding and exerting inhibitory activity via a mixed-type mechanism. These results provide an important basis for developing novel, low-toxicity, multi-target anti-diabetic drugs from edible and medicinal fungi.