Human neutrophil elastase inhibitory alkaloids from chelidonium majus L

Abstract

Human neutrophil elastase (HNE) represents a good therapeutic target for the treatment of inflammatory diseases as well as invasion of microorganism. The methanol extract of a aerial part of Chelidonium majus L. showed high activity against the neutrophil elastase with an IC50 value of 100 μg/mL. Due to its potency, subsequent bioactivity-guided fractionation of methanol extract led to six alkaloids (1-6), which were identified as dihydrosanguinarine (1), (s)-stylopine (2), arnottianamide (3), (+)-chelidonine (4), spallidamine (5), and N-transferuloyltyramine (6). Among of them, three alkaloids (2, 5, and 6) inhibited HNE in a dose-dependent manner with IC50 ranging between 11.6 and 51.0 μM. Lineweaver-Burk and Dixon plots, and their secondary replots showed that alkaloids (2, 5, and 6) were mixed inhibitors of HNE. The analysis of KI and KIS value proved that all inhibitors (2, 5, and 6) had reversible mixed type I mechanism.