title: The effect of sesquiterpene lactones on the release of human neutrophil elastase.
abstract: Sesquiterpene lactones (SLs) are natural products responsible for the anti-inflammatory activity of a variety of medicinal plants, mainly from the Asteraceae family. Here, we investigated whether they also influence the process of exocytosis of pro-inflammatory enzymes, such as the human neutrophil elastase (HNE). Altogether, eight structurally different SLs from the eudesmanolide, guaianolide, pseudoguaianolide, and germacranolide type were studied. Neutrophils were isolated from fresh human blood. After pre-incubation with different concentrations of the respective SL and cytochalasin B, the exocytosis of elastase was initiated either by platelet activating factor or N-formyl-methionyl-leucyl-phenylalanine. Inhibition of HNE release was measured by p-nitroaniline formation. The SLs exhibited an inhibitory effect on elastase release from neutrophils challenged either by platelet activating factor or N-formyl-methionyl-leucyl-phenylalanine. Concentration-response curves were recorded and the IC(50) values ranged from 2 to 30 microM. Studies on isolated HNE showed that a selective direct inhibition on HNE can be excluded. Interestingly, the inhibitory activity did not correlate with the number of alpha,beta-unsaturated carbonyl functions. The structure-activity relationship and the molecular mechanism are discussed.
authors.affiliation: Institut für Pharmazeutische Biologie, Universität Freiburg, Stefan-Meier-Str. 19, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Siedle
authors.forename: Linda
authors.initials: L
authors.lastname: Gustavsson
authors.forename: Senia
authors.initials: S
authors.lastname: Johansson
authors.forename: Renato
authors.initials: R
authors.lastname: Murillo
authors.forename: Victor
authors.initials: V
authors.lastname: Castro
authors.forename: Lars
authors.initials: L
authors.lastname: Bohlin
authors.forename: Irmgard
authors.initials: I
authors.lastname: Merfort
mesh_terms: D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D019272:Leukocyte Elastase / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D012717:Sesquiterpenes / Q000737:chemistry
chemical_list: D007783:Lactones; D012717:Sesquiterpenes; D019272:Leukocyte Elastase