Human neutrophil elastase inhibitory potential of flavonoids from Campylotropis hirtella and their kinetics

Abstract

Campylotropis hirtella is used as a food supplement in the subtropical region of China. In an intensive hunt for human neutrophil elastase inhibitors, we isolated eight flavonoids from C. hirtella three of which (1-3) emerged to be elastase inhibitors. Geranylated flavonoids (1-3) displayed significant inhibitory activity with IC(50)s between 8.5 and 30.8 mu M. The most striking example was geranylated isofavanone 3 that inhibited elastase significantly (IC50 = 30.8 mu M) but its parent compound (dalbergioidin) and isoflavone analog (5) were inactive (IC50 > 200 mu M). Compounds (1-3) displayed different kinetic mechanisms (noncompetitive, competitive, and mixed type, respectively) that were dependent upon the parent skeleton. The competitive inhibitor, isoflavan-3-ol-4-one 2 manifested an inhibition of isomerization profile for elastase with kinetic parameters K-5 = 0.0386 M-1 S-1, K-6 = 0.0244 mu M-1 S-1 and K-i(app) = 16.3427 mu M. The specific identification of metabolites was accomplished by LC-DAD-ESI/MS that was also used to analyze abundance of active components (1-3) within the plant.