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

Inflamm Allergy Drug Targets. 2015;14(1):37-46. doi: 10.2174/1871528114666151005125120.

Abstract

Context: 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.

Materials and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Carrageenan / administration & dosage
  • Coumarins / administration & dosage*
  • Disease Models, Animal
  • Down-Regulation
  • Female
  • Humans
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Mice
  • NF-kappa B / metabolism*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Plant Extracts / administration & dosage*
  • Pleurisy / chemically induced
  • Pleurisy / drug therapy*
  • Pleurisy / immunology
  • Polygala / immunology
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • 5-hydroxy-6-methoxy-7-(3-methyl-but-2-enyloxy)-2H-1-benzopyran-2-one
  • Anti-Inflammatory Agents
  • Coumarins
  • Interleukin-1beta
  • NF-kappa B
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • Carrageenan
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • p38 Mitogen-Activated Protein Kinases