Li_2025_Bioorg.Chem_168_109328

Obesity is consistently associated with dysregulated glycolipid metabolism. The regulation of alpha-amylase and pancreatic lipase plays a pivotal role in maintaining glucose and lipid homeostasis. In this study, we demonstrated that Osmanthus fragrans flower phenylethanoid glycoside-rich extract (OFE) effectively suppressed alpha-amylase activity through mixed-type inhibition and pancreatic lipase activity via competitive inhibition. Molecular docking analysis revealed that acteoside and salidroside bond to the amino acid residues of these enzymes primarily through hydrogen bonding and hydrophobic effect. Further investigation using UV-vis and fluorescence spectroscopy indicated that acteoside interacted with alpha-amylase via static quenching and with pancreatic lipase through dynamic quenching. Interestingly, while acteoside quenched the fluorescence of both enzymes, salidroside enhanced their fluorescence. Circular dichroism spectroscopy analysis showed distinct structural effects: acteoside increased alpha-helix and beta-sheet content while reducing beta-turn and random coil structures, whereas salidroside elevated alpha-helix and beta-sheet content but decreased beta-turn and random coil formation. Our findings demonstrate that acteoside and salidroside are effective natural inhibitors of alpha-amylase and pancreatic lipase, supporting the potential of Osmanthus fragrans flower as a dietary intervention for glycolipid metabolism disorders.