姜黄素、水飞蓟素和松香酸对胰脂肪酶的不同抑制机制：比较多光谱和分子动力学模拟研究

Pancreatic lipase (PL) is a key enzyme in dietary lipid digestion, and its inhibition is a critical strategy for limiting intestinal lipid absorption. Natural bioactive compounds are promising and safe PL inhibitors. However, the molecular interaction mechanisms and differential inhibitory effects of curcumin (CUR), silymarin (SM), and abietic acid (AA) toward PL remain poorly elucidated, restricting their application in lipid regulation. To fill this gap, this study investigated the inhibitory activities and molecular mechanisms of CUR, SM, and AA toward PL. Enzyme inhibition kinetics verified that all three compounds acted as reversible PL inhibitors. Fluorescence spectra showed that they quenched PL intrinsic fluorescence in a concentration-dependent manner and altered the microenvironments of tyrosine and tryptophan residues, with SM exerting the strongest quenching effect and AA the weakest. Quenching kinetics and thermodynamic analyses further demonstrated a static quenching mechanism, characterized by spontaneous and exothermic binding, predominantly driven by hydrogen bonding and van der Waals interactions. The binding stoichiometry was mainly 1:1, with a temperature-dependent deviation observed for AA. Molecular dynamics simulations supported the stable binding of all three compounds within the PL active pocket, with SM exhibiting the highest binding affinity. These findings clarify the distinct mechanisms of CUR, SM, and AA toward PL and provide a basis for their application in lipid regulation and functional food development.