Matricin / matricine
Fitoterapia. 2015 Oct;106:122-8. doi: 10.1016/j.fitote.2015.08.010. Epub 2015 Aug 21.
Revisited anti-inflammatory activity of matricine in vitro: Comparison with chamazulene.
Flemming M1, Kraus B1, Rascle A2, Jürgenliemk G1, Fuchs S3, Fürst R3, Heilmann J4.
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.
Chamazulene is formed from matricine in the gut of rats by the action of gastric acid following oral administration. When volunteers were given matricine orally (500 mg, in suspension), peak plasma levels of chamazulene carboxylic acid were determined at 0.9 to 2.2 μg/mL.