Quinic acid as an inhibitor of α‐glucosidase activity, nonenzymatic glycosylation, and glucose transport in Caco‐2 cells

Abstract Hyperglycemia and diabetes are common metabolic disorders. It is considered a safe and effective strategy to screen active ingredients from food and herbs for controlling blood sugar levels. Quinic acid (QA) is a natural polyphenolic acid with various health‐promoting properties. In this study, QA was found to exhibit a potent inhibitory effect on α‐glucosidase activity, with a half maximal inhibitory concentration (IC 50 ) of 5.46 mM. This inhibitory property surpassed that of three common organic acids including gallic acid, malic acid, and citric acid. A combination of 25% acarbose (0.5 mM) and 75% QA (5 mM) (v/v) exhibited synergistic inhibition of α‐glucosidase activity. Enzyme kinetics, fluorescence spectra, and molecular docking analyses indicated that QA acted as an uncompetitive inhibitor of α‐glucosidase, with hydrogen bonds playing a key role in the intermolecular interactions. Moreover, QA was found to effectively inhibit three major nonenzymatic glycation products including advanced glycosylation end products (AGEs), fructosamine, and α‐dicarbonyl in a dose‐dependent manner, outperforming the positive control aminoguanidine (AG) within the tested concentration range. Utilizing a Caco‐2 cell model, QA demonstrated the ability to inhibit the transmembrane absorption of glucose. This study highlighted QA as a promising food functional factor that had been overlooked in the past, offering potential benefits in improving hyperglycemia, diabetes, and associated complications through the inhibition of α‐glucosidase, nonenzymatic glycosylation, and glucose uptake.