title: Pinosylvin and monomethylpinosylvin, constituents of an extract from the knot of Pinus sylvestris, reduce inflammatory gene expression and inflammatory responses in vivo.
abstract: Scots pine (Pinus sylvestris) is known to be rich in phenolic compounds, which may have anti-inflammatory properties. The present study investigated the anti-inflammatory effects of a knot extract from P. sylvestris and two stilbenes, pinosylvin and monomethylpinosylvin, isolated from the extract. Inflammation is characterized by increased release of pro-inflammatory and regulatory mediators including nitric oxide (NO) produced by the inducible nitric oxide synthase (iNOS) pathway. The knot extract (EC50 values of 3 and 3 μg/mL) as well as two of its constituents, pinosylvin (EC50 values of 13 and 15 μM) and monomethylpinosylvin (EC50 values of 8 and 12 μM), reduced NO production and iNOS expression in activated macrophages. They also inhibited the production of inflammatory cytokines IL-6 and MCP-1. More importantly, pinosylvin and monomethylpinosylvin exerted a clear anti-inflammatory effect (80% inhibition at the dose of 100 mg/kg) in the standard in vivo model, carrageenan-induced paw inflammation in the mouse, with the effect being comparable to that of a known iNOS inhibitor L-NIL. The results reveal that the Scots pine stilbenes pinosylvin and monomethylpinosylvin are potential anti-inflammatory compounds.
authors.affiliation: †The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere FI-33014, 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 FI-33014, 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 FI-33014, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Leppänen
authors.affiliation: ‡Process Chemistry Centre, Laboratory of Wood and Paper Chemistry, Åbo Akademi University, Turku/Åbo FI-20500, Finland.
authors.forename: Christer
authors.initials: C
authors.lastname: Eckerman
authors.affiliation: ‡Process Chemistry Centre, Laboratory of Wood and Paper Chemistry, Åbo Akademi University, Turku/Åbo FI-20500, Finland.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Holmbom
authors.affiliation: †The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere FI-33014, Finland.
authors.forename: Eeva
authors.initials: E
authors.lastname: Moilanen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002351:Carrageenan; D002460:Cell Line; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors; D015870:Gene Expression / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D041605:Pinus sylvestris / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology; D013267:Stilbenes / Q000302:isolation & purification / Q000494:pharmacology*; D014934:Wood / Q000737:chemistry; D000093242:Interleukin-6 Inhibitors; D000094162:Phytoalexins
chemical_list: D000893:Anti-Inflammatory Agents; D002351:Carrageenan; D018932:Chemokine CCL2; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D010936:Plant Extracts; D013267:Stilbenes; D000093242:Interleukin-6 Inhibitors; C000601858:monomethylpinosylvin; C049032:pinosylvin; D000094162:Phytoalexins
keywords: HO-1; Pinus sylvestris; anti-inflammatory; iNOS; stilbene