Human neutrophil elastase (HNE) inhibitory polyprenylated acylphloroglucinols from the flowers of Hypericum ascyron

In the course of an investigation of human neutrophil elastase (HNE) associated with inflammation, the extract of the flower parts of Hypericum ascyron showed a significant influence to HNE. The responsible metabolites to HNE inhibition were found to be eight polyprenylated acylphloroglucinols, PPAPs (1-8) which showed IC50 ranges between 2.4 and 19.9 mu M. This is the first report to demonstrate that PPAP skeleton exhibits potent HNE inhibition. The compounds 1-3 were characterized and newly named as ascyronone E (IC50=4.3 mu M), ascyronone F (IC50=19.9 mu M), ascyronone G (IC50=4.5 mu M) based on 2D-NMR spectroscopic data. In the kinetic analysis of double reciprocal plots, all the compounds showed noncompetitive behaviors to HNE enzyme with the remaining of K-m and the increase of V-max. The binding affinity levels (K-SV) by using fluorescence were sufficient to be able to prove that PPAPs (1-8) had compliant interaction with inhibitory potencies.