title: Revisited anti-inflammatory activity of matricine in vitro: Comparison with chamazulene.
abstract: The proazulene matricine (1) is present in chamomile flower heads and has been proven to exhibit strong in vivo anti-inflammatory activity. In contrast to other secondary metabolites in chamomile preparations like its degradation product chamazulene (2), no plausible targets have been found to explain this activity. Therefore we revisited 1 regarding its in vitro anti-inflammatory activity in cellular and molecular studies. Using ICAM-1 as a marker for NF-κB activation, it was shown that ICAM-1 protein expression induced by TNF-α and LPS, but not by IFN-γ, was remarkably inhibited by 1 in endothelial cells (HMEC-1). Inhibition was concentration-dependent in a micromolar range (10-75 μM) and did not involve cytotoxic effects. At 75 μM expression of the adhesion molecule ICAM-1 was down to 52.7 ± 3.3% and 20.4 ± 1.8% of control in TNF-α and LPS-stimulated HMEC-1, respectively. In contrast, 2 showed no activity. Quantitative RT-PCR experiments revealed that TNF-α-induced expression of the ICAM-1 gene was also reduced by 1 in a concentration-dependent manner, reaching 32.3 ± 6.2% of control at 100 μM matricine. Additional functional assays (NF-κB promotor activity and cytoplasm to nucleus translocation) confirmed the inhibitory effect of 1 on NF-κB signaling. Despite the fact that 1 lacks an α,β-unsaturated carbonyl and is thus not able to act via a Michael reaction with electron rich SH groups of functional biological molecules, data gave strong evidence that 1 inhibits NF-κB transcriptional activity in endothelial cells by an hitherto unknown mechanism and this may contribute to its well-known anti-inflammatory activity in vivo.
authors: Institut für Pharmazie, Universität Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany.
authors: Marcel
authors: M
authors: Flemming
authors: Institut für Pharmazie, Universität Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany.
authors: Birgit
authors: B
authors: Kraus
authors: Institut für Immunologie, Universität Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
authors: Anne
authors: A
authors: Rascle
authors: Institut für Pharmazie, Universität Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany.
authors: Guido
authors: G
authors: Jürgenliemk
authors: Institut für Pharmazeutische Biologie, Goethe-Universität Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany.
authors: Simone
authors: S
authors: Fuchs
authors: Institut für Pharmazeutische Biologie, Goethe-Universität Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany.
authors: Robert
authors: R
authors: Fürst
authors: Institut für Pharmazie, Universität Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany. Electronic address: joerg.heilmann@chemie.uni-regensburg.de.
authors: Jörg
authors: J
authors: Heilmann
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D052176:Azulenes / Q000494:pharmacology*; D002478:Cells, Cultured; D020843:Chamomile / Q000737:chemistry; D042783:Endothelial Cells / Q000187:drug effects*; D035264:Flowers / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D045789:Sesquiterpenes, Guaiane; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D052176:Azulenes; D007783:Lactones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; C039959:matricin; C013872:chamazulene
keywords: Anti-inflammatory activity; Chamazulene; ICAM-1; Matricaria recutita; Matricine; NF-κB