3-deoxysilybin exerts anti-inflammatory effects by suppressing NF-κB activation in lipopolysaccharide-stimulated RAW264.7 macrophages

Biosci Biotechnol Biochem. 2014;78(12):2051-8. doi: 10.1080/09168451.2014.948377. Epub 2014 Aug 8.

Abstract

3-deoxysilybin (3-DS), also known as (-)-isosilandrin A, is a natural flavonoid of Silybum marianum. This study was designed to investigate the anti-inflammatory effect and the underlying molecular mechanisms of 3-DS in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. 3-DS dose-dependently inhibited the production of NO and the expression of iNOS in LPS-stimulated RAW264.7 macrophages. 3-DS also inhibited the production of pro-inflammatory cytokines (MCP-1, TNF-α, IL-6, and IL-1β) in LPS-stimulated RAW264.7 macrophages. Moreover, 3-DS decreased the NF-κB DNA binding activity in LPS-stimulated RAW264.7 macrophages. Furthermore, 3-DS suppressed NF-κB activation by inhibiting the degradation of IκBα and nuclear translocation of p65 subunit of NF-κB in LPS-stimulated RAW264.7 macrophages. Taken together, the present study suggests for the first time that 3-DS may exhibit an anti-inflammatory effect through the suppression of NF-κB transcriptional activation in LPS-stimulated RAW264.7 macrophages.

Keywords: 3-deoxysilybin; NF-κB; NO; iNOS; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / isolation & purification
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Line, Transformed
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Dioxanes / isolation & purification
  • Dioxanes / pharmacology*
  • Flavanones / isolation & purification
  • Flavanones / pharmacology*
  • Flavonoids / isolation & purification
  • Flavonoids / pharmacology*
  • Gene Expression Regulation
  • I-kappa B Proteins / genetics
  • I-kappa B Proteins / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / pharmacology*
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Plant Extracts / chemistry
  • Signal Transduction
  • Silybum marianum / chemistry*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • 3-deoxysilybin
  • Anti-Inflammatory Agents, Non-Steroidal
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Dioxanes
  • Flavanones
  • Flavonoids
  • I-kappa B Proteins
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Nfkbia protein, mouse
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse