title: Costunolide and Dehydrocostuslactone, two natural sesquiterpene lactones, ameliorate the inflammatory process associated to experimental pleurisy in mice.
abstract: The aim of this study was to investigate the effect of costunolide (CS) and dehydrocostuslactone (DCE) a well-known sesquiterpene lactones contained in many plants, in a model of lung injury induced by carrageenan administration in the mice. Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by fluid accumulation in the pleural cavity which contained a large number of polymorphonuclear cells (PMNs) as well as an infiltration of PMNs in lung tissues and increased production of tumour necrosis factor α (TNF-α). All parameters of inflammation were attenuated by CS and DCE (15mg/kg 10% DMSO i.p.) administered 1h before carrageenan. Carrageenan induced an up regulation of the intracellular adhesion molecules-1 (ICAM-1) and P-selectin, as well as nitrotyrosine and poly (ADP-ribose) (PAR) as determined by immunohistochemical analysis of lung tissues. The degree of staining for the ICAM-1, P-selectin, nitrotyrosine and PAR was reduced by CS and DCE. Additionally we show that this inflammatory events were associated with NF-κB and STAT3 activation and these sesquiterpenes down-regulated it. Taken together, ours results clearly shown that CS and DCE may offer a novel therapeutic approach for the management of inflammatory diseases.
authors.affiliation: Department of Life and Reproduction Sciences, Section of Biochemistry, University of Verona, Verona, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Butturini
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, 98166 Messina, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.affiliation: Department of Life and Reproduction Sciences, Section of Biochemistry, University of Verona, Verona, Italy.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, 98166 Messina, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Paterniti
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, 98166 Messina, Italy.
authors.forename: Akbar
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Department of Life and Reproduction Sciences, Section of Biochemistry, University of Verona, Verona, Italy. Electronic address: sofia.mariotto@univr.it.
authors.forename: Sofia
authors.initials: S
authors.lastname: Mariotto
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, 98166 Messina, Italy; Manchester University, Manchester, United Kingdom. Electronic address: salvator@unime.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002351:Carrageenan / Q000009:adverse effects; D004195:Disease Models, Animal; D007783:Lactones / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis
chemical_list: D000893:Anti-Inflammatory Agents; D007783:Lactones; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D012717:Sesquiterpenes; C002744:3-nitrotyrosine; D014443:Tyrosine; C083030:dehydrocostus lactone; C002602:costunolide; D002351:Carrageenan; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases
keywords: Costunolide; Dehydrocostuslactone; Inflammation; NF-κB; Peroxynitrite; STAT3