title: In vivo and in vitro anti-inflammatory activity of neorogioltriol, a new diterpene extracted from the red algae Laurencia glandulifera.
abstract: Neorogioltriol is a tricyclic brominated diterpenoid isolated from the organic extract of the red algae Laurencia glandulifera. In the present study, the anti-inflammatory effects of neorogioltriol were evaluated both in vivo using carrageenan-induced paw edema and in vitro on lipopolysaccharide (LPS)-treated Raw264.7 macrophages. The in vivo study demonstrated that the administration of 1 mg/kg of neorogioltriol resulted in the significant reduction of carregeenan-induced rat edema. In vitro, our results show that neorogioltriol treatment decreased the luciferase activity in LPS-stimulated Raw264.7 cells, stably transfected with the NF-κB-dependent luciferase reporter. This effect on NF-κB activation is not mediated through MAPK pathways. The inhibition of NF-κB activity correlates with decreased levels of LPS-induced tumor necrosis factor-alpha (TNFα) present in neorogioltriol treated supernatant cell culture. Further analyses indicated that this product also significantly inhibited the release of nitric oxide and the expression of cyclooxygenase-2 (COX-2) in LPS-stimulated Raw264.7 cells. These latter effects could only be observed for neorogioltriol concentrations below 62.5 μM. To our knowledge, this is the first report describing a molecule derived from Laurencia glandulifera with anti-inflammatory activity both in vivo and in vitro. The effect demonstrated in vitro may be explained by the inhibition of the LPS-induced NF-κB activation and TNFα production. NO release and COX-2 expression may reinforce this effect.
authors.affiliation: Unit of Biotoxines, Pasteur Institut of Tunis, 13, Place Pasteur, B.P. 74. 1002 Tunis-Belvedere, Tunisia.
authors.forename: Rim
authors.initials: R
authors.lastname: Chatter
authors.affiliation: Laboratory of Immunopathology, Vaccinology and Molecular Genetics (LIVGM), WHO Collaborating Center for Research and Training in Leishmaniasis and International Associated Laboratory (LIA-CNRS), Pasteur Institut of Tunis, 13, Place Pasteur, B.P. 74. 1002 Tunis Belvedere, Tunisia.
authors.forename: Rym Ben
authors.initials: RB
authors.lastname: Othman
authors.affiliation: Laboratory of Immunopathology, Vaccinology and Molecular Genetics (LIVGM), WHO Collaborating Center for Research and Training in Leishmaniasis and International Associated Laboratory (LIA-CNRS), Pasteur Institut of Tunis, 13, Place Pasteur, B.P. 74. 1002 Tunis Belvedere, Tunisia.
authors.forename: Sameh
authors.initials: S
authors.lastname: Rabhi
authors.affiliation: Department of Pharmacognosy and Chemistry of Natural Products, School of Pharmacy, University of Athens, Panepistimiopolis Zografou, Athens 15771, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Kladi
authors.affiliation: Unit of Biotoxines, Pasteur Institut of Tunis, 13, Place Pasteur, B.P. 74. 1002 Tunis-Belvedere, Tunisia.
authors.forename: Safa
authors.initials: S
authors.lastname: Tarhouni
authors.affiliation: Department of Pharmacognosy and Chemistry of Natural Products, School of Pharmacy, University of Athens, Panepistimiopolis Zografou, Athens 15771, Greece.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Vagias
authors.affiliation: Department of Pharmacognosy and Chemistry of Natural Products, School of Pharmacy, University of Athens, Panepistimiopolis Zografou, Athens 15771, Greece.
authors.forename: Vassilios
authors.identifier: 0000-0001-9856-4725
authors.initials: V
authors.lastname: Roussis
authors.affiliation: Laboratory of Immunopathology, Vaccinology and Molecular Genetics (LIVGM), WHO Collaborating Center for Research and Training in Leishmaniasis and International Associated Laboratory (LIA-CNRS), Pasteur Institut of Tunis, 13, Place Pasteur, B.P. 74. 1002 Tunis Belvedere, Tunisia.
authors.forename: Lamia
authors.initials: L
authors.lastname: Guizani-Tabbane
authors.affiliation: Unit of Biotoxines, Pasteur Institut of Tunis, 13, Place Pasteur, B.P. 74. 1002 Tunis-Belvedere, Tunisia.
authors.forename: Riadh
authors.initials: R
authors.lastname: Kharrat
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D001168:Arthritis / Q000188:drug therapy; D001241:Aspirin / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D035061:Control Groups; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004224:Diterpenes / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000502:physiology; D044722:Laurencia / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000378:metabolism / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D010936:Plant Extracts; C569845:neorogioltriol; D003907:Dexamethasone; D001241:Aspirin