Inhibition of lipoxygenase by ellagic acid: Insights from multi-spectroscopic techniques and molecular docking

Lipoxygenase (LOX)-induced endogenous lipid peroxidation significantly contributes to food nutrient loss and flavor deterioration. This study aimed to investigate the inhibitory mechanism of ellagic acid (EA) on LOX by integrating enzyme kinetics, multi-spectroscopic techniques, and molecular docking. The results showed that EA inhibited LOX in a dose-dependent manner, achieving an inhibition rate of 87.73% at 600 μg/mL and an IC₅₀ of 20.84 μg/mL. The inhibition was identified as mixed-type competitive inhibition. EA effectively quenched the endogenous fluorescence of LOX through static quenching, and the association constant increased with rising temperature. Thermodynamic parameters suggested that the formation of the EA-LOX complex was spontaneous and endothermic, primarily driven by hydrophobic interactions. EA preferentially interacted with tryptophan residues, inducing changes in the microenvironment and secondary structure of LOX. Additionally, an increase in the average particle size confirmed complex formation. The molecular docking results were consistent with the spectroscopic experiments, providing a possible microscopic mechanism for the maintenance of the three-dimensional conformation of the complex through hydrophobic interactions and hydrogen bonding. This study provides a theoretical foundation for the use of EA to regulate LOX activity and highlights its promising application in food quality preservation.