Abstract
Elastase, a serine protease, has been implicated in chronic obstructive pulmonary disease and systemic inflammatory response syndrome. In this study, we evaluated the effects of phillyrin and phillygenin, 2 major Forsythia lignans, on elastase inhibition. Both compounds exhibited competitive inhibition, as confirmed by enzymatic kinetics, spectroscopy, and molecular docking. Phillygenin exhibited stronger activity (IC(50) 0.5 mmol/L, K (i) 4.0 × 10(-4) mol/L) than phillyrin (IC(50) 1.5 mmol/L, K (i) 9.7 × 10(-4) mol/L), likely due to reduced steric hindrance. Spectroscopic analysis revealed ligand-induced conformational changes in elastase, characterized by increased α-helix and random coil content and decreased β-sheet structures. Docking revealed interactions involving π-cation, π-sigma, hydrogen bonds, hydrophobic forces, electrostatics, and van der Waals effects. These results provide mechanistic insights into the inhibitory effects of phillyrin and phillygenin and highlight their potential as therapeutic agents for elastase-related diseases.