(E)-1-(4-ethoxyphenyl)-3-(4-nitrophenyl)-prop-2-en-1-one suppresses LPS-induced inflammatory response through inhibition of NF-κB signaling pathway

Int Immunopharmacol. 2013 Apr;15(4):743-51. doi: 10.1016/j.intimp.2013.02.024. Epub 2013 Mar 14.

Abstract

Flavonoids are a class of compounds that exist in nature with the structure of 2-phenyl-chromone. In Chinese traditional medicine, herbal drugs containing flavonoids are widely used for the treatment of inflammation, cardiovascular disease, tumor and so on. In this study, we investigated the anti-inflammatory effect and related mechanisms of a novel synthetic flavonoid, (E)-1-(4-ethoxyphenyl)-3-(4-nitrophenyl)-prop-2-en-1-one (ETH) in lipopolysaccharide (LPS) stimulated macrophages. Our results showed that ETH inhibited LPS-induced TNF-α and IL-6 release in a dose-dependent manner, and decreased TNF-α, IL-1β, IL-6 and iNOS mRNA production. LPS-induced expression of cyclooxygenase-2 (COX-2) was also significantly attenuated by ETH. Pretreatment with ETH reduced the I-κBα phosphorylation, p65 nuclear translocation as well as NF-κB-dependent transcriptional activity. In addition, ETH exhibited a significant protection against LPS-induced inflammatory mortality in mice. Taken together, these findings suggest that ETH can inhibit LPS-induced inflammation via suppressing NF-κB signaling pathway, indicating that ETH may be a potential anti-inflammatory agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Blotting, Western
  • Cell Culture Techniques
  • Cell Line
  • Cell Survival / drug effects
  • Chalcones / chemistry
  • Chalcones / pharmacology*
  • Dose-Response Relationship, Drug
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Interleukin-1beta / genetics
  • Interleukin-6 / genetics
  • Lipopolysaccharides / toxicity*
  • Macrophages / drug effects
  • Macrophages / immunology
  • Male
  • Medicine, Chinese Traditional
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Molecular Structure
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / biosynthesis
  • Nitric Oxide Synthase Type II / genetics
  • Protein Transport
  • Real-Time Polymerase Chain Reaction
  • Shock, Septic / prevention & control
  • Signal Transduction / drug effects*
  • Survival Analysis
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • 1-(4-ethoxyphenyl)-3-(4-nitrophenyl)-prop-2-en-1-one
  • Anti-Inflammatory Agents, Non-Steroidal
  • Chalcones
  • Flavonoids
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • lipopolysaccharide, E coli O55-B5
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse