AUTHOR=Yao Mengli , Liu Jia , Zhou Fang , Li Haizhi , Wang Ruoyong , Han Zhong , Liu Jie , Chen Wei , Liu Guoyu , Yang Shuheng , Duan Shenlin , Han Xiaofeng , Yuan Peng TITLE=α-Glucosidase inhibitory activity of polyphenol-rich sugarcane extract: screening and mechanistic insights based on biolayer interferometry-mass spectrometry JOURNAL=Frontiers in Nutrition VOLUME=Volume 12 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1575409 DOI=10.3389/fnut.2025.1575409 ISSN=2296-861X ABSTRACT=IntroductionPolyphenol-rich sugarcane extract (PRSE) contains bioactive compounds with potential hypoglycemic properties, but its direct interaction with α-glucosidase has not been explored.MethodsThis study investigated the inhibitory mechanism of PRSE on α-glucosidase using enzyme kinetics. Bioactive compounds with α-glucosidase-binding affinity were identified through biolayer interferometry-mass spectrometry (BLI-MS), and the binding mechanisms were further explored via molecular docking analysis.Results and discussionPRSE was found to inhibit α-glucosidase through a mixed-type mechanism. A total of 29 compounds, including 4 coumarins, 9 phenolic acids, and 16 flavonoids, were identified in the PRSE dissociation solution. Representative compounds included coumarin, kaempferol, apigenin 7-o-neohesperidoside, and vicenin 3. Notably, apigenin 7-o-neohesperidoside and vicenin 3 were identified for the first time as potential α-glucosidase inhibitors.These compounds interacted with key residues of α-glucosidase, such as Asp and Glu, via hydrogen bonding, π-anion interactions, and hydrophobic forces. These findings suggest that PRSE could serve as a promising natural source of α-glucosidase inhibitors. The application of BLI-MS proved effective for screening target bioactive compounds in plant extracts. PRSE may have potential applications in functional foods for postprandial glycemic control and type 2 diabetes prevention.