| Texto completo | |
| Autor(es): |
Silva, Rangel L.
[1]
;
Lopes, Alexandre H.
[1]
;
Franca, Rafael O.
[1]
;
Vieira, Silvio M.
[1, 2]
;
Silva, Ellen C. C.
[2]
;
Amorim, Rodrigo C. N.
[2]
;
Cunha, Fernando Q.
[1]
;
Pohlit, Adrian M.
[2]
;
Cunha, Thiago M.
[1]
Número total de Autores: 9
|
| Afiliação do(s) autor(es): | [1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Sao Paulo - Brazil
[2] Natl Inst Amazon Res INPA, Manaus, Amazonas - Brazil
Número total de Afiliações: 2
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Journal of Natural Products; v. 78, n. 2, p. 241-249, FEB 2015. |
| Citações Web of Science: | 10 |
| Resumo | |
Isobrucein B (1) is a quassinoid isolated from the Amazonian medicinal plant Picrolemma sprucei. Herein we investigate the anti-inflammatory and antihyperalgesic effects of this quassinoid. Isobrucein B (1) (0.5-5 mg/kg) inhibited carrageenan-induced inflammatory hyperalgesia in mice in a dose-dependent manner. Reduced hyperalgesia was associated with reduction in both neutrophil migration and pronociceptive cytokine production. Pretreatment with 1 inhibited in vitro production/release of cytokines TNF, IL-1 beta, and KC/CXCL1 by lipopolysaccharide-stimulated macrophages. To investigate its molecular mechanism, RAW 264.7 macrophages with a luciferase reporter gene controlled by the NF-kappa B promoter were used (RAW 264.7-Luc). Quassinoid 1 reduced the luminescence emission by RAW 264.7-Luc stimulated by different compounds. Unexpectedly, NF-kappa B translocation to macrophage nuclei was not inhibited by 1 when evaluated by Western blotting and immunofluorescence. Furthermore, quassinoid 1 did not change the levels of TNF mRNA transcription in stimulated macrophages, suggesting post-transcriptional modulation. In addition, constitutive expression of luciferase in RAW 264.7 cells transiently transfected with a plasmid containing a universal promoter was inhibited by 1. Thus, isobrucein B (1) displays anti-inflammatory and antihyperalgesic activities by nonselective post-transcriptional modulation, resulting in decreased production/release of pro-inflammatory cytokines and neutrophil migration. (AU) | |
| Processo FAPESP: | 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias |
| Beneficiário: | Fernando de Queiroz Cunha |
| Modalidade de apoio: | Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs |