The Effects of 1- O -Acetylbritannilactone Isolated from Inula britannica Flowers on Human Neutrophil Elastase and Inflammation of RAW 264.7 Cells and Zebrafish Larvae

During a search for natural inflammatory inhibitors, 1- -acetylbritannilactone (ABL), a sesquiterpene lactone, was isolated from the flowers of . ABL significantly inhibited human neutrophil elastase (HNE) with a half-maximal inhibitory concentration (IC ) of 3.2 ± 0.3 µM, thus did so more effectively than the positive control material (epigallocatechin gallate) (IC 7.2 ± 0.5 µM). An enzyme kinetic study was performed. ABL noncompetitively inhibited HNE with an inhibition constant of 2.4 µM. ABL inhibited lipopolysaccharide-induced nitric oxide and prostaglandin E production by RAW 264.7 cells in a dose-dependent manner, as well as the protein-level expression of inducible nitric oxide synthase and cyclooxygenase-2. The anti-inflammatory effect of ABL was confirmed using a transgenic Tg( :EGFP) zebrafish larval model. The exposure of the larvae to ABL inhibited neutrophil recruitment to the site of injury after tail fin amputation.