PUBLICATION

Rhein attenuates inflammation through inhibition of NF-κB and NALP3 inflammasome in vivo and in vitro

Authors
Ge, H., Tang, H., Liang, Y., Wu, J., Yang, Q., Zeng, L., Ma, Z.
ID
ZDB-PUB-170628-7
Date
2017
Source
Drug design, development and therapy   11: 1663-1671 (Journal)
Registered Authors
Keywords
COX-2, NALP3, NF-κB, iNOS, inflammatory, rhein, zebrafish
MeSH Terms
  • Adenosine Triphosphate/pharmacology
  • Animals
  • Animals, Genetically Modified
  • Anthraquinones/pharmacology*
  • Anti-Inflammatory Agents/pharmacology*
  • Cell Movement/drug effects
  • Cyclooxygenase 2/metabolism
  • Dose-Response Relationship, Drug
  • Inflammasomes/drug effects*
  • Inflammasomes/immunology
  • Inflammasomes/metabolism
  • Inflammation/immunology
  • Inflammation/metabolism
  • Inflammation/prevention & control*
  • Inflammation Mediators/metabolism
  • Interleukin-1beta/metabolism
  • Lipopolysaccharides/pharmacology
  • Macrophage Activation/drug effects*
  • Macrophages/drug effects*
  • Macrophages/immunology
  • Macrophages/metabolism
  • Mice
  • NF-kappa B/immunology
  • NF-kappa B/metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein/immunology
  • NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
  • Nitric Oxide/metabolism
  • Nitric Oxide Synthase Type II/metabolism
  • Phosphorylation
  • RAW 264.7 Cells
  • Signal Transduction/drug effects
  • Transcription Factor RelA/metabolism
  • Zebrafish/genetics
PubMed
28652704 Full text @ Drug Des Devel Ther
Abstract
Rhein is an important component in traditional Chinese herbal medicine formulations for gastrointestinal disorders, including inflammatory bowel diseases such as ulcerative colitis. In this study, we investigated the beneficial effects of rhein in inflammation models in the transgenic zebrafish line TG (corolla eGFP), in which both macrophages and neutrophils express eGFP and RAW264.7 macrophages. We found that the tail-cutting-induced migration of immune cells was significantly reduced in transgenic zebrafish treated with rhein. In addition, the production of proinflammatory cytokines, including IL-6, IL-1β, and tumor necrosis factor-α, were significantly reduced in lipopolysaccharide (LPS)-induced RAW264.7 macrophages treated with rhein. Parallel to the inhibition of proinflammatory cytokines, rhein significantly reduced phosphorylation levels of NF-κB p65 and inducible nitric oxide synthase, as well as COX-2 protein expression levels. Furthermore, rhein significantly reduced NALP3 and cleaved IL-1β expression in LPS + ATP-induced RAW264.7 macrophages. Thus, the present study demonstrates that rhein may exhibit its anti-inflammatory action via inhibition of NF-κB and NALP3 inflammasome pathways.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
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Mapping