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|Título:||The Quassinoid Isobrucein B Reduces Inflammatory Hyperalgesia and Cytokine Production by Post-transcriptional Modulation|
|Autor(es):||SILVA, RANGEL L.|
LOPES, ALEXANDRE H.
FRANÇA, RAFAEL O.
VIEIRA, SÍLVIO M.
Silva, Ellen C. C.
AMORIM, RODRIGO C. N.
CUNHA, FERNANDO Q.
Adrian Martin Pohlit
CUNHA, THIAGO M.
|Revista:||Journal of Natural Products|
|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-1β, 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-κB promoter were used (RAW 264.7-Luc). Quassinoid 1 reduced the luminescence emission by RAW 264.7-Luc stimulated by different compounds. Unexpectedly, NF-κB 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.|
|Aparece nas coleções:||Coordenação de Tecnologia e Inovação (COTI)|
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