title: Anti-inflammatory Effects of Nortrachelogenin in Murine J774 Macrophages and in Carrageenan-Induced Paw Edema Model in the Mouse.
abstract: Nortrachelogenin is a pharmacologically active lignan found in knot extracts ofPinus sylvestris. In previous studies, some lignans have been shown to have anti-inflammatory properties, which made nortrachelogenin an interesting candidate for our study. In inflammation, bacterial products and cytokines induce the expression of inducible nitric oxide synthase, cyclooxygenase-2, and microsomal prostaglandin E synthase-1. These enzymes synthesize factors, which, together with proinflammatory cytokines, are important mediators and drug targets in inflammatory diseases.The effects of nortrachelogenin on the expression of inducible nitric oxide synthase, cyclooxygenase-2, and microsomal prostaglandin E synthase-1 as well as on the production of nitric oxide, prostaglandin E2, and cytokines interleukin-6 and monocyte chemotactic protein-1 were investigated in the murine J774 macrophage cell line. In addition, we examined the effect of nortrachelogenin on carrageenan-induced paw inflammation in mice.Interestingly, nortrachelogenin reduced carrageenan-induced paw inflammation in mice and inhibited the production of inflammatory factors nitric oxide, prostaglandin E2, interleukin-6, and monocyte chemotactic protein-1 in J774 macrophagesin vitro. Nortrachelogenin inhibited microsomal prostaglandin E synthase-1 protein expression but had no effect on cyclooxygenase-2 protein levels. Nortrachelogenin also had a clear inhibitory effect on inducible nitric oxide synthase protein expression but none on its mRNA levels, and the proteasome inhibitor lactacystin reversed the effect of nortrachelogenin on inducible nitric oxide synthase expression, suggesting a post-transcriptional mechanism of action.The results revealed hitherto unknown anti-inflammatory properties of nortrachelogenin, which could be utilized in the development of anti-inflammatory treatments.
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: Mirka
authors.initials: M
authors.lastname: Laavola
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Leppänen
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Eräsalo
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Hämäläinen
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: Riina
authors.initials: R
authors.lastname: Nieminen
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: Eeva
authors.initials: E
authors.lastname: Moilanen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D002351:Carrageenan / Q000009:adverse effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D005663:Furans / Q000737:chemistry / Q000494:pharmacology*; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D041605:Pinus sylvestris / Q000737:chemistry*; D061988:Proteasome Inhibitors / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D005663:Furans; D017705:Lignans; D061988:Proteasome Inhibitors; D009569:Nitric Oxide; C020436:nortrachelogenin; D002351:Carrageenan; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse