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Molecules 2015, 20(2), 2636-2657; doi:10.3390/molecules20022636

Effect of Gedunin on Acute Articular Inflammation and Hypernociception in Mice

1
Laboratório de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro 21041-250, Brazil
2
Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina 86057-970, Brazil
3
Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto 14049-900, Brazil
4
Centro de Desenvolvimento Tecnológico em Saúde, CDTS/INCT-IDN, Fundação Oswaldo Cruz, Rio de Janeiro 21045-360, Brazil
These authors contributed equally to this work.
These authors are considered last authors.
*
Author to whom correspondence should be addressed.
Academic Editor: Nancy D. Turner
Received: 19 December 2014 / Revised: 15 January 2015 / Accepted: 24 January 2015 / Published: 3 February 2015
(This article belongs to the Collection Bioactive Compounds)
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Abstract

Gedunin, a natural limonoid from Meliaceae species, has been previously described as an antiinflammatory compound in experimental models of allergic inflammation. Here, we report the antiinflammatory and antinociceptive effects of gedunin in an acute model of articular inflammation induced by zymosan (500 μg/cavity; intra-articular) in C57BL/6 mice. Intraperitoneal (i.p.) pretreatment with gedunin (0.005–5 mg/kg) impaired zymosan-induced edema formation, neutrophil accumulation and hypernociception in mouse knee joints, due to decreased expression of preproET-1 mRNA and production of LTB4, PGE2, TNF-α and IL-6. Mouse post-treatment with gedunin (0.05 mg/kg; i.p.) 1 and 6 h after stimulation also impaired articular inflammation, by reverting edema formation, neutrophil accumulation and the production of lipid mediators, cytokines and endothelin. In addition, gedunin directly modulated the functions of neutrophils and macrophages in vitro. The pre-incubation of neutrophil with gedunin (100 µM) impaired shape change, adhesion to endothelial cells, chemotaxis and lipid body formation triggered by different stimuli. Macrophage pretreatment with gedunin impaired intracellular calcium mobilization, nitric oxide production, inducible nitric oxide synthase expression and induced the expression of the antiinflammatory chaperone heat shock protein 70. Our results demonstrate that gedunin presents remarkable antiinflammatory and anti-nociceptive effects on zymosan-induced inflamed knee joints, modulating different cell populations. View Full-Text
Keywords: zymosan; arthritis; edema; neutrophil; macrophage; lipid body; cytokine; leukotriene; prostaglandin zymosan; arthritis; edema; neutrophil; macrophage; lipid body; cytokine; leukotriene; prostaglandin
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Conte, F.P.; Ferraris, F.K.; Costa, T.E.M.M.; Pacheco, P.; Seito, L.N.; Verri, W.A., Jr.; Cunha, F.Q.; Penido, C.; Henriques, M.G. Effect of Gedunin on Acute Articular Inflammation and Hypernociception in Mice. Molecules 2015, 20, 2636-2657.

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