This study investigated the maturation-dependentα-glucosidase inhibitory(AGI)potential of metabolites in two nonpungent Capsicum annuum cultivars,“Meein”and“Dangjo,”using an integrated approach that combined meta...This study investigated the maturation-dependentα-glucosidase inhibitory(AGI)potential of metabolites in two nonpungent Capsicum annuum cultivars,“Meein”and“Dangjo,”using an integrated approach that combined metabolomics,molecular docking,and in vitro enzyme assays.UPLC-Orbitrap-MS-based metabolite profiling of fruits at different ripening stages revealed distinct metabolite profiles with varying AGI activities.Multivariate statistical analyses,including partial least squares regression and Pearson's correlation,identified 37 metabolites,particularly phenolic compounds,that were significantly correlated with AGI activity(P<0.05,VIP>1.5);several have limited prior evidence directly linking them toα-glucosidase inhibition.Molecular docking simu-lations predicted strong binding affinities between these metabolites andα-glucosidase,primarily driven by hydrogen bonding and van der Waals interactions.These predictions were supported by in vitro AGI activity assays using pure metabolite standards,in which caffeic acid showed the strongest inhibitory activity(IC_(50)=10.86μmol/L),outperforming the reference inhibitor acarbose(IC_(50)=17.26μmol/L).Sinapinic and 3-hydroxy-butyric acids also demonstrated significant AGI potential,with their combined use further enhancing the inhibitory effect(IC_(50)=6.98μmol/L).Lineweaver-Burk kinetic analysis revealed distinct modes of inhibition:competitive inhibition by 3-hydroxybutyric acid;noncompetitive inhibition by 3-hydroxybenzoic acid and 4,7-dihydroxycoumarin;and mixed-type inhibition by caffeic and sinapinic acids.In silico secondary structure analysis further confirmed the specificity of the ligand-enzyme interactions.Overall,these findings highlight the potential of naturally occurring C.annuum phenolic metabolites as powerfulα-glucosidase inhibitors and suggest they could serve as natural alternatives to synthetic antidiabetic drugs for managing postprandial hyperglycemia.展开更多
基金supported by the Korea Basic Science Institute(National Research Facilities and Equipment Center)grant funded by the Ministry of Education(grant no.RS-2023-NF001356)the Regional Innovation System&Education(RISE)through theSeoul RISE Center,funded by the Ministry of Education(MOE)and the Seoul Metropolitan Government(2025-RISE-01-019-04)+3 种基金the Cooperative Research Pro-gram for Agricultural Science and Technology Development(RS-2024-00322321)of the Rural Development Administration(RDA)the Basic Science Research Program(RS-2023-00208020)the National Research Foundation of Koreaand the Sejong University Sabbatical Research Program.
文摘This study investigated the maturation-dependentα-glucosidase inhibitory(AGI)potential of metabolites in two nonpungent Capsicum annuum cultivars,“Meein”and“Dangjo,”using an integrated approach that combined metabolomics,molecular docking,and in vitro enzyme assays.UPLC-Orbitrap-MS-based metabolite profiling of fruits at different ripening stages revealed distinct metabolite profiles with varying AGI activities.Multivariate statistical analyses,including partial least squares regression and Pearson's correlation,identified 37 metabolites,particularly phenolic compounds,that were significantly correlated with AGI activity(P<0.05,VIP>1.5);several have limited prior evidence directly linking them toα-glucosidase inhibition.Molecular docking simu-lations predicted strong binding affinities between these metabolites andα-glucosidase,primarily driven by hydrogen bonding and van der Waals interactions.These predictions were supported by in vitro AGI activity assays using pure metabolite standards,in which caffeic acid showed the strongest inhibitory activity(IC_(50)=10.86μmol/L),outperforming the reference inhibitor acarbose(IC_(50)=17.26μmol/L).Sinapinic and 3-hydroxy-butyric acids also demonstrated significant AGI potential,with their combined use further enhancing the inhibitory effect(IC_(50)=6.98μmol/L).Lineweaver-Burk kinetic analysis revealed distinct modes of inhibition:competitive inhibition by 3-hydroxybutyric acid;noncompetitive inhibition by 3-hydroxybenzoic acid and 4,7-dihydroxycoumarin;and mixed-type inhibition by caffeic and sinapinic acids.In silico secondary structure analysis further confirmed the specificity of the ligand-enzyme interactions.Overall,these findings highlight the potential of naturally occurring C.annuum phenolic metabolites as powerfulα-glucosidase inhibitors and suggest they could serve as natural alternatives to synthetic antidiabetic drugs for managing postprandial hyperglycemia.
