Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Identification of molecular targets of the oligomeric non-prenylated acylphloroglucinols from Myrtus communis and their implication as anti-inflammatory compounds

Abstract

Myrtucommulone (MC) and semi-myrtucommulone (S-MC) are unique, oligomeric, non-prenylated acylphloroglucinols contained in the leaves of myrtle (Myrtus communis L.). Although extracts of myrtle have been traditionally used in folk medicine for the treatment of various disorders, studies addressing select cellular or molecular pharmacological properties of these extracts, or specific ingredients thereof, are rare. Here we show for the first time that MC and S-MC potently suppress the biosynthesis of eicosanoids by direct inhibiting cyclooxygenase-1 and 5-lipoxygenase in vitro and in vivo at IC50 values in the range of 1.8 to 29 microM. Moreover, we show that MC and S-MC prevent the mobilization of Ca(2+) in polymorphonuclear leukocytes, mediated by G protein signalling pathways at IC50 values of 0.55 and 4.5 microM, respectively, and suppress the formation of reactive oxygen species (ROS) and the release of elastase at comparable concentrations. The isobutyrophenone core of MC and S-MC was much less potent or even not active at all. Also, MC or S-MC only partially inhibited peroxide formation or failed to block Ca(2+) mobilization and elastase release when PMNL were challenged with ionomycin that circumvents G protein signalling for cell activation. We conclude, that in view of their ability to suppress typical proinflammatory cellular responses, the unique acylphloroglucinols MC and S-MC from myrtle may possess an anti-inflammatory potential, suggesting their therapeutic use for the treatment of diseases related to inflammation and allergy.