Plant phenolics inhibit neutrophil elastase.
Human neutrophil elastase (HNE) is a serine protease, which is present in its active form in inflamed tissue as well as in psoriatic lesions. In extension of our research on natural compounds as inhibitors of HNE or of its release, several phenolics of different size were tested. The ellagitannins agrimoniin and pedunculagin were the most potent direct HNE inhibitors (IC (50) = 0.9 and 2.8 microM, respectively). Ligand docking calculations provided evidence that inhibition may occur in an unspecific manner. Agrimoniin also showed anti-proliferative effects in the ATP assay (IC (50) = 3.2 microM), suggesting that this type of tannin could have beneficial effects in the treatment of diseases such as psoriasis. Tests with other phenolics combined with ligand docking experiments revealed that, besides the presence of ORTHO-dihydroxy groups, a specific lipophilic shape is necessary for an inhibitory activity. The phenolic genistein deserves special interest as an inhibitor of elastase release because its effect was remarkably potent (IC (50) = 0.6 microM).
Hrenn
Andrea
A
Institute for Pharmaceutical Sciences, Department of Pharmaceutical Biology and Biotechnology, University of Freiburg, Freiburg, Germany.
Steinbrecher
Thomas
T
Labahn
Andreas
A
Schwager
Joseph
J
Schempp
Christoph M
CM
Merfort
Irmgard
I
D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D010636:Phenols / Q000494:pharmacology*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry*; D053491:Proteinase Inhibitory Proteins, Secretory / Q000032:analysis*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology
D047348:Hydrolyzable Tannins; D010636:Phenols; D010936:Plant Extracts; D053491:Proteinase Inhibitory Proteins, Secretory; D013267:Stilbenes; C011867:4-hydroxyphenylethanol; C052420:agrimoniin; D002392:Catechin; C045651:epigallocatechin gallate; D019833:Genistein; D019272:Leukocyte Elastase; D010626:Phenylethyl Alcohol; D000077185:Resveratrol