Abstract
Myrtucommulone (MC) and semimyrtucommulone (S-MC) are unique oligomeric, nonprenylated acylphloroglucinols contained in the leaves of myrtle (Myrtus communis). 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 μM. Moreover, we show that MC and S-MC prevent the mobilization of Ca2+ in polymorphonuclear leukocytes, mediated by G protein signaling pathways at IC50 values of 0.55 and 4.5 μM, respectively, and suppress the formation of reactive oxygen species and the release of elastase at comparable concentrations. The isobutyrophenone core of MC as well as S-MC was much less potent or even not active at all. In addition, MC or S-MC only partially inhibited peroxide formation or failed to block Ca2+ mobilization and elastase release when polymorphonuclear leukocytes were challenged with ionomycin that circumvents G protein signaling 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.
Footnotes
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This work was supported by the Deutsche Forschungsgemeinschaft (Grant GRK 137/3) and by the Beilstein-Institut zur Förderung der Chemischen Wissenschaften.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.105.090720.
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ABBREVIATIONS: MC, myrtucommulone; S-MC, semimyrtucommulone; ROS, reactive oxygen species; GPCR, G protein-coupled receptor; LO, lipoxygenase; COX, cyclooxygenase; LT, leukotriene; PG, prostaglandin; AA, arachidonic acid; IBP-C, isobutyrophenone core; DMSO, dimethyl sulfoxide; fMLP, N-formyl-methionyl-leucyl-phenylalanine; DCF-DA, 2′,7′-dichlorofluorescein diacetate; PMNL, polymorphonuclear leukocyte; PBS, phosphate-buffered saline; PGC buffer, PBS containing 1 mg/ml glucose and 1 mM CaCl2; rt, room temperature; 12-HHT, 12(S)-hydroxy-5-cis-8,10-trans-heptadecatrienoic acid; HPLC, high-performance liquid chromatography; MM6, Mono Mac 6; LPS, lipopolysaccharide; U-73122, 1-[6-[[17β-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione; AM, acetoxymethyl ester; A2767, adenosine 5′-triphosphate-agarose.
- Received June 7, 2005.
- Accepted July 8, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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