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 IC₅₀s between 8.5 and 30.8 μM. The most striking example was geranylated isofavanone 3 that inhibited elastase significantly (IC₅₀=30.8 μM) but its parent compound (dalbergioidin) and isoflavone analog (5) were inactive (IC₅₀>200 μM). 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 K₅=0.0386 M⁻¹S⁻¹, K₆=0.0244 μM⁻¹S⁻¹ and K_i^app = 16.3427 μM. 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.

Keywords:

• Camplyotropis hirtella
• competitive inhibition
• geranylated isoflavanone
• human neutrophil elastase
• LC-DAD-ESI/MS

Declaration of interest

The authors declared that there are not conflicts of interest. The research was supported by a grant Next-Generation BioGreen 21 program (SSAC, NO. PJ01107001), Rural development Administration, Republic of Korea. All students were supported by a scholarship from the BK21 plus program.

Supplementary material available online