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INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Myrtucommulone from Myrtus communis Exhibits Potent Anti-Inflammatory Effectiveness in Vivo

Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy (C.P., L.S.); Istituto di Ricovero e Cura a Carattere Scientifico Centro Neurolesi "Bonino-Pulejo," Messina, Italy (A.R., R.D.P., E.M., T.G., P.B., S.C.); Departments of Human Pathology (R.C.) and Clinical and Experimental Medicine and Pharmacology (S.C.), School of Medicine, University of Messina, Messina, Italy; and Department of Pharmaceutical Analytics, Pharmaceutical Institute, University Tübingen, Tübingen, Germany (C.P., A.K., O.W.)

Myrtucommulone (MC), a nonprenylated acylphloroglucinol contained in the leaves of myrtle (Myrtus communis), has been reported to suppress the biosynthesis of eicosanoids by inhibition of 5-lipoxygenase and cyclooxygenase-1 in vitro and to inhibit the release of elastase and the formation of reactive oxygen species in activated polymorphonuclear leukocytes. Here, in view of the ability of MC to suppress typical proinflammatory cellular responses in vitro, we have investigated the effects of MC in in vivo models of inflammation. MC was administered to mice intraperitoneally, and paw edema and pleurisy were induced by the subplantar and intrapleural injection of carrageenan, respectively. MC (0.5, 1.5, and 4.5 mg/kg i.p.) reduced the development of mouse carrageenan-induced paw edema in a dose-dependent manner. Moreover, MC (4.5 mg/kg i.p. 30 min before and after carrageenan) exerted anti-inflammatory effects in the pleurisy model. In particular, 4 h after carrageenan injection in the pleurisy model, MC reduced: 1) the exudate volume and leukocyte numbers; 2) lung injury (histological analysis) and neutrophil infiltration (myeloperoxidase activity); 3) the lung intercellular adhesion molecule-1 and P-selectin immunohistochemical localization; 4) the cytokine levels (tumor necrosis factor- and interleukin-1β) in the pleural exudate and their immunohistochemical localization in the lung; 5) the leukotriene B₄, but not prostaglandin E₂, levels in the pleural exudates; and 6) lung peroxidation (thiobarbituric acid-reactant substance) and nitrotyrosine and poly (ADP-ribose) immunostaining. In conclusion, our results demonstrate that MC exerts potent anti-inflammatory effects in vivo and offer a novel therapeutic approach for the management of acute inflammation.

Address correspondence to: Salvatore Cuzzocrea, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Via C. Valeria, 5-98125 Messina, Italy. E-mail: salvator{at}unime.it