The quassinoid isobrucein B reduces inflammatory hyperalgesia and cytokine production by post-transcriptional modulation.

Abstract

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.

• Authors: Rangel L Silva, Alexandre H Lopes, Rafael O França, Sílvio M Vieira, Ellen C C Silva, Rodrigo C N Amorim, Fernando Q Cunha, Adrian M Pohlit, Thiago M Cunha
• Journal: Journal of natural products (J Nat Prod) Vol. 78 Issue 2 Pg. 241-9 (Feb 27 2015) ISSN: 1520-6025 [Electronic] United States
• PMID: 25667960 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• I-kappa B Proteins
• Interleukin-1beta
• Lipopolysaccharides
• NF-kappa B
• Quassins
• Tumor Necrosis Factor-alpha
• Nitric Oxide
• isobrucein B
• Carrageenan
• Peroxidase
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• Mitogen-Activated Protein Kinases
• Dinoprostone

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Brazil
• Carrageenan (adverse effects)
• Cyclooxygenase 2 (metabolism)
• Cytokines (metabolism)
• Dinoprostone (metabolism)
• Hyperalgesia (drug therapy)
• I-kappa B Proteins (drug effects)
• Inflammation (chemically induced)
• Interleukin-1beta (metabolism)
• Lipopolysaccharides (pharmacology)
• Macrophages (drug effects)
• Male
• Mice
• Mitogen-Activated Protein Kinases (metabolism)
• Molecular Structure
• NF-kappa B (metabolism)
• Nitric Oxide (biosynthesis)
• Nitric Oxide Synthase Type II (antagonists & inhibitors)
• Peroxidase (metabolism)
• Plants, Medicinal (chemistry)
• Quassins (chemistry, pharmacology)
• Simaroubaceae (chemistry)
• Tumor Necrosis Factor-alpha (drug effects)