# Comparative inhibitory effects of phillyrin and phillygenin on elastase: mechanisms and therapeutic potential

## TL;DR

This study compares how two compounds from Forsythia inhibit elastase, a protease linked to lung and inflammatory diseases, and finds that phillygenin is more effective.

## Contribution

The study reveals the molecular mechanisms and relative efficacy of phillyrin and phillygenin as elastase inhibitors.

## Key findings

- Phillygenin showed stronger elastase inhibition than phillyrin with lower IC50 and Ki values.
- Spectroscopy showed ligand-induced structural changes in elastase, including increased α-helix and random coil content.
- Molecular docking identified multiple interaction types, including π-cation, hydrogen bonds, and hydrophobic forces.

## 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 (IC50 0.5 mmol/L, Ki 4.0 × 10−4 mol/L) than phillyrin (IC50 1.5 mmol/L, Ki 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.

Diagram illustrating enzyme activity and interaction studies. Left: Lineweaver-Burk plots analyzing enzyme kinetics. Center: Chemical structures and a protein model labeled for activity evaluation. Right: Graphs showing interaction measurements, including spectra and protein structure representations, emphasizing structural changes and binding activity.