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