Differential hypoglycemic effects and underlying mechanisms of A-type and B-type oligomeric proanthocyanidins

Proanthocyanidins (PCs) may lower blood sugar, but activity differences between A-type and B-type oligomers remain unclear. This study compared A-type (PA1, PA2) and B-type (PB1, PB2) oligomeric PCs using enzyme inhibition, molecular docking, and insulin-resistant HepG2 cells. A-type PCs exhibited stronger α-glucosidase inhibition, whereas B-type PCs showed superior α-amylase inhibitory activity. All components enhanced glucose consumption and reduced oxidative stress and inflammation. B-type PCs more potently activated the IRS-1/PI3K/Akt pathway, AMPK, and the Nrf2/HO-1/NQO1 antioxidant axis. In conclusion, A-type PCs excel in direct α-glucosidase inhibition, whereas B-type PCs play a superior role in improving insulin signaling and antioxidant defense in vitro. These findings provide a structure-activity basis for developing targeted functional products, pending in vivo validation.