Inhibition of Human Neutrophil Elastase by Sesquiterpene Lactone Dimers from the Flowers of Inula britannica.

A new sesquiterpene lactone dimer [1], together with five known compounds (2-6), was isolated from the flowers of Inula britannica. The structures of these compounds were established by extensive spectroscopic studies and chemical evidence. The inhibitory activities of these isolated compounds (1-6) against human neutrophil elastase (HNE) were also evaluated in vitro; compounds 1 and 6 exhibited significant inhibitory effects against HNE activity, with IC50 values of 8.2 and 10.4 μM, respectively, comparable to that of epigallocatechin gallate (EGCG; IC50 = 10.9 μM). In addition, compounds 3 and 5 exhibited moderate HNE inhibitory effects, with IC50 values of 21.9 and 42.5 μM, respectively. In contrast, compounds 2 and 4 exhibited no such activity (IC50 ＞ 100 μM). The mechanism by which 1 and 3 inhibited HNE was noncompetitive inhibition, with inhibition constant (Ki) values of 8.0 and 22.8 μM, respectively.