title: Myrtucommulone from Myrtus communis exhibits potent anti-inflammatory effectiveness in vivo.
abstract: 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-alpha and interleukin-1beta) in the pleural exudate and their immunohistochemical localization in the lung; 5) the leukotriene B(4), but not prostaglandin E(2), 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.
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico Centro Neurolesi Bonino-Pulejo, Messina, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Rossi
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Tiziana
authors.initials: T
authors.lastname: Genovese
authors.forename: Rocco
authors.initials: R
authors.lastname: Caminiti
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.forename: Carlo
authors.initials: C
authors.lastname: Pergola
authors.forename: Andreas
authors.initials: A
authors.lastname: Koeberle
authors.forename: Oliver
authors.initials: O
authors.lastname: Werz
authors.forename: Lidia
authors.initials: L
authors.lastname: Sautebin
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015153:Blotting, Western; D002351:Carrageenan; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D004487:Edema / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D005528:Foot / Q000473:pathology; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D031651:Myrtus / Q000737:chemistry*; D019007:P-Selectin / Q000096:biosynthesis; D009195:Peroxidase / Q000378:metabolism; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D010998:Pleurisy / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D053583:Interleukin-1beta; D019007:P-Selectin; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; C455139:myrtucommulone A; D018799:Intercellular Adhesion Molecule-1; D007975:Leukotriene B4; D002351:Carrageenan; D010696:Phloroglucinol; D009195:Peroxidase; D051546:Cyclooxygenase 2; D015232:Dinoprostone