Targeted Screening of α‐Glucosidase Inhibitory Phenolic Monomers in Highland Barley

ABSTRACT Background and Objectives Highland barley polyphenols demonstrate potent α‐glucosidase inhibitory activity, showcasing their potential in regulating postprandial glucose homeostasis. However, the key phenolic monomer responsible for this hypoglycemic effect remains to be systematically investigated. Findings Comprehensive metabolomic profiling of highland barley polyphenol extract revealed 25 phenolic monomers. These compounds underwent molecular docking against human and yeast α‐glucosidase. The docking results identified nine phenolic monomers with superior binding affinities. In vitro assays revealed that quercetin, apigenin, and phloretin exhibited the highest α‐glucosidase inhibitory activity. Moreover, starch digestion assays demonstrated that supplementing highland barley whole flour with these phenolic monomers (1%, 3%, 5%, w/w) led to a dose‐dependent reduction in starch digestibility, specifically reducing the content of rapidly digestible starch (RDS) and increasing resistant starch (RS). Conclusions Quercetin, apigenin, and phloretin are identified as the key phenolic monomers in highland barley responsible for effective α‐glucosidase inhibition and modulation of starch digestibility. Significance and Novelty The findings provide a theoretical basis for functional food formulations utilizing these natural phenolic monomers as α‐glucosidase inhibitors.