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
Volume: 14
Issue: 1
Author(s): Marcus Vinicius Pereira dos Santos Nascimento, Fábio Arruda-Silva, Ana Beatriz G. Luz, Dalila Venzke, Gustavo S. Queiroz, Beatriz G. Mendes, Eduardo R. Fernandes-Ribeiro, Tânia S. Fröde, Moacir G. Pizzolatti and Eduardo M. Dalmarco
Affiliation:
Keywords:
Airway inflammation, anti-inflammatory, 7-prenyloxi-6-methoxycoumarin, coumarins, NF-κB, p38 MAPK,
pleurisy.
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.