Inhibition of the NF-κB and p38 MAPK pathways by scopoletin reduce the inflammation caused by carrageenan in the mouse model of pleurisy.
Natural products have long been used worldwide as therapeutic agents, but it is only recently, in response to the new challenges posed by global population aging, that interest in research into potentially therapeutic natural products has reemerged. In this context, coumarins, chemical compounds found in plants that have known anti-inflammatory activity, are promising candidates for the development of new drugs. In this study we test the effect of scopoletin, a coumarin found in several plant species, on carrageenan-induced inflammation in the mouse model of pleurisy. Initially, the effects of scopoletin on leukocyte migration and exudate concentrations were evaluated at three different doses (0.1, 1 and 5 mg/kg) and time (0.5-4 h before pleurisy). In the next step, we chose the lowest dose capable of inhibiting the inflammatory parameters (1 mg/kg), in order to analyze the myeloperoxidase and adenosine deaminase activities, the nitric oxide, tumor necrosis factor-α, and interleukin 1β levels in the fluid leakage, and the p65 subunit of NF-κB and p38 MAPK phosphorylation. Scopoletin at a dose of 1 mg/kg was able to significantly reduce cell migration and exudation to the pleural fluid (p < 0.01). Scopoletin at the same dose also decreased the myeloperoxidase and adenosine-deaminase activities and nitric oxide, tumor necrosis factor-α, and interleukin-1β levels (p < 0.01). In addition, it significantly reduced p65 and p38 phosphorylation in the mouse lungs (p < 0.01). Our results reinforce that scopoletin has important anti-inflammatory activity, and shows, that this effect can be attributed to the ability of this compound to inhibit the phosphorylation of NF-κB and p38 MAPK.
a Department of Clinical Analysis , Centre of Health Sciences, Federal University of Santa Catarina, Campus Universitário - Trindade , Florianopolis , SC , Brazil ;
Marcus Vinicius
MV
Pereira Dos Santos Nascimento
b Department of Pathology and Diagnostics, Division of General Pathology , University of Verona , Verona , Italy ;
Fábio
F
Arruda-Silva
a Department of Clinical Analysis , Centre of Health Sciences, Federal University of Santa Catarina, Campus Universitário - Trindade , Florianopolis , SC , Brazil ;
Ana Beatriz
AB
Gobbo Luz
a Department of Clinical Analysis , Centre of Health Sciences, Federal University of Santa Catarina, Campus Universitário - Trindade , Florianopolis , SC , Brazil ;
Bruna
B
Baratto
c Department of Chemistry, Centre of Physical and Mathematical Sciences , Federal University of Santa Catarina, Campus Universitário - Trindade , Florianopolis , SC , Brazil ;
Dalila
D
Venzke
a Department of Clinical Analysis , Centre of Health Sciences, Federal University of Santa Catarina, Campus Universitário - Trindade , Florianopolis , SC , Brazil ;
Beatriz Garcia
BG
Mendes
a Department of Clinical Analysis , Centre of Health Sciences, Federal University of Santa Catarina, Campus Universitário - Trindade , Florianopolis , SC , Brazil ;
Tânia Silvia
TS
Fröde
c Department of Chemistry, Centre of Physical and Mathematical Sciences , Federal University of Santa Catarina, Campus Universitário - Trindade , Florianopolis , SC , Brazil ;
Moacir
M
Geraldo Pizzolatti
a Department of Clinical Analysis , Centre of Health Sciences, Federal University of Santa Catarina, Campus Universitário - Trindade , Florianopolis , SC , Brazil ;|d Department of Molecular Biotechnology and Health Sciences , Molecular Biotechnology Center, University of Torino , Torino , Italy.
Eduardo Monguilhott
EM
Dalmarco
D000818:Animals; D002351:Carrageenan / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000276:immunology*; D010998:Pleurisy / Q000139:chemically induced* / Q000188:drug therapy* / Q000276:immunology; D012603:Scopoletin / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology*
D016328:NF-kappa B; D002351:Carrageenan; D048051:p38 Mitogen-Activated Protein Kinases; D012603:Scopoletin
Airway inflammation; anti-inflammatory; mice; pleurisy; scopoletin