Rutin prevents inflammation induced by lipopolysaccharide in RAW 264.7 cells via conquering the TLR4-MyD88-TRAF6-NF-κB signalling pathway

J Pharm Pharmacol. 2021 Mar 1;73(1):110-117. doi: 10.1093/jpp/rgaa015.

Abstract

Objectives: Inflammation widely exists in many diseases and poses a great threat to human and animal health. Rutin, quercetin-3-rhamnosyl glucoside, has a variety of pharmacological effects, including anti-oxidant, anti-inflammatory, antibacterial, anticancer and radioresistance effects. The current study focused on evaluation of its anti-inflammatory activity and described the mechanism of rutin in lipopolysaccharide-induced RAW 264.7 cells.

Methods: The related gene and protein expression levels were investigated by quantification real-time PCR and western blotting, respectively.

Key findings: This study revealed that rutin can decrease inducible nitric oxide synthase (iNOS) gene and protein expression levels, effectively increase IκB gene expression, reduce toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), tumour necrosis factor receptor-associated factor 6 (TRAF6) and p65 gene expression and inhibit the phosphorylation of IκB and p65 and the proteins expression of TLR4, MyD88 and TRAF6.

Conclusions: These results suggest that rutin might exert anti-inflammatory effect on LPS-stimulated RAW 264.7 cells and will be potentially useful as an adjuvant treatment for inflammatory diseases.

Keywords: TLR4-MyD88-TRAF6-NF-κB; anti-inflammatory; lipopolysaccharide; rutin; signalling pathway.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Inflammation* / chemically induced
  • Inflammation* / prevention & control
  • Lipopolysaccharides
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Myeloid Differentiation Factor 88 / metabolism*
  • NF-kappa B / metabolism*
  • Phosphorylation
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • RAW 264.7 Cells
  • Rutin / pharmacology*
  • Rutin / therapeutic use
  • Signal Transduction
  • TNF Receptor-Associated Factor 6 / metabolism*
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Lipopolysaccharides
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Plant Extracts
  • TNF Receptor-Associated Factor 6
  • TRAF6 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Rutin