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 (IC₅₀) 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.