The effect of sesquiterpene lactones on the release of human neutrophil elastase

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...

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Bibliographic Details
Published in:Biochemical pharmacology 2003-03, Vol.65 (5), p.897-903
Main Authors: Siedle, Bettina, Gustavsson, Linda, Johansson, Senia, Murillo, Renato, Castro, Victor, Bohlin, Lars, Merfort, Irmgard
Format: Article
Language:English
Subjects:
Anti-inflammatory activity
Biological and medical sciences
Bones, joints and connective tissue. Antiinflammatory agents
FARMACI
fMLP
Human neutrophil elastase release
Humans
Lactones - chemistry
Lactones - pharmacology
Leukocyte Elastase - metabolism
Medical sciences
Neutrophil granulocytes
Neutrophils - drug effects
Neutrophils - enzymology
PAF
Pharmacology. Drug treatments
PHARMACY
Sesquiterpene lactones
Sesquiterpenes - chemistry
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Summary: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 μM. 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 α,β-unsaturated carbonyl functions. The structure–activity relationship and the molecular mechanism are discussed.
ISSN:0006-2952
1356-1839
1873-2968
DOI:10.1016/S0006-2952(02)01652-0