title: 7-prenyloxi-6-methoxycoumarin from Polygala sabulosa A.W. Bennett Regulates p38 MAPK and NF-kB Pathways Inhibiting the Inflammation Induced by Carrageenan in the Mouse Model of Pleurisy.
abstract: BACKGROUND
  Polygala sabulosa, popularly known as "timutu-pinheirinho," has been used in Brazilian folk medicine for the treatment of bowel and kidney disorders and as an expectorant.
  
  
  OBJECTIVE
  Evaluate the anti-inflammatory effects of the crude extract (CE), acetonic fraction (Ac), and the main compound, 7-prenyloxi-6-methoxycoumarin (PC) on a mouse model of carrageenan-induced pleurisy.
  
  
  METHODS
  A mouse model of carrageenan-induced pleurisy was used to investigate the effects of P. sabulosa CE, Ac and PC on leukocyte migration, exudate formation, activities of myeloperoxidase (MPO), and adenosine-deaminase (ADA), levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and nitric oxide (NO). In addition, the effect of the plant material on lung histology was also evaluated. The effects of PC on the TNF-α, IL-1β and NO synthase 2 (NOS2) mRNA expression, were also investigated. Finally, the effect of PC on the nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (p38 MAPK) was also evaluated.
  
  
  RESULTS
  CE, Ac and PC reduced inflammation in the pleural cavity and lungs. This effect was evidenced by reduction on all inflammatory parameters evaluated; the exception being the inability of the CE to inhibit exudate formation. In isolation, PC showed reduction on mRNA levels of TNF-α, IL-1β and NOS2, and on activation of the NF-κB and p38 MAPK pathways.
  
  
  CONCLUSIONS
  The presented results show that P. sabulosa has significant anti-inflammatory activity, as does its main compound, PC. Moreover, the results suggest that PC exerts its effects mainly by inhibited the NF-κB and p38 MAPK pathways.
authors.forename: Marcus Vinicius Pereira
authors.initials: MV
authors.lastname: Dos Santos Nascimento
authors.forename: Fábio
authors.initials: F
authors.lastname: Arruda-Silva
authors.forename: Ana Beatriz G
authors.initials: AB
authors.lastname: Luz
authors.forename: Dalila
authors.initials: D
authors.lastname: Venzke
authors.forename: Gustavo S
authors.initials: GS
authors.lastname: Queiroz
authors.forename: Beatriz G
authors.initials: BG
authors.lastname: Mendes
authors.forename: Eduardo R
authors.initials: ER
authors.lastname: Fernandes-Ribeiro
authors.forename: Tânia S
authors.initials: TS
authors.lastname: Fröde
authors.forename: Moacir G
authors.initials: MG
authors.lastname: Pizzolatti
authors.affiliation: Department of Clinical Analyses, Centre of Health Sciences, Federal University of Santa Catarina, Campus Universitário - Trindade, 88040-970, Florianopolis, SC, Brazil. eduardo.dalmarco@ufsc.br.
authors.forename: Eduardo M
authors.initials: EM
authors.lastname: Dalmarco
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002351:Carrageenan / Q000008:administration & dosage; D003374:Coumarins / Q000008:administration & dosage*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage*; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D031801:Polygala / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C436726:5-hydroxy-6-methoxy-7-(3-methyl-but-2-enyloxy)-2H-1-benzopyran-2-one; D000893:Anti-Inflammatory Agents; D003374:Coumarins; D053583:Interleukin-1beta; D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D002351:Carrageenan; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases