Blue Honeysuckle (Lonicera caerulea L.) Polyphenol Extract Inhibits α-Glucosidase Activity and Modulates Glucose Transport in Caco-2 Cells

Blue honeysuckle (Lonicera caerulea L.) is a polyphenol-rich berry increasingly recognized as a functional food ingredient for postprandial glycemic management. However, it remains unclear whether its polyphenols can modulate intestinal glucose transport in addition to inhibiting carbohydrate-digesting enzymes. In this study, blue honeysuckle polyphenol extract (BHPE) was characterized by UPLC-QTOF-MS/MS, and its effects on α-glucosidase activity and intestinal glucose transport were evaluated using enzyme kinetics, fluorescence quenching, molecular docking, and differentiated Caco-2 monolayers. A total of 24 phenolic compounds were tentatively identified, with anthocyanins and chlorogenic acid derivatives as the major constituents. BHPE exhibited a mixed-type, static-quenching inhibition of α-glucosidase (IC50 = 75.05 μg/mL). Furthermore, molecular docking revealed that key constituents, including cyanidin-3-O-glucoside, chlorogenic acid, and proanthocyanidin B1, bind the enzyme via hydrogen bonding and hydrophobic interactions. In Caco-2 cell monolayers, BHPE reduced glucose transport by up to 51.56% under simulated postprandial conditions and coordinately downregulated SGLT1 and GLUT2 mRNA expression to 0.58- and 0.51-fold, respectively. These findings extend the bioactivity profile of blue honeysuckle polyphenols from enzyme-level inhibition to functional regulation at the intestinal epithelial barrier, highlighting their potential as multi-target natural ingredients for the attenuation of postprandial hyperglycemia.