(E)-3-(3,4-dihydroxy-2-methoxyphenyl)-1-(2,4-dihydroxyphenyl)prop-2-en-1-one, a novel licochalcone B derivative compound, suppresses lipopolysaccharide-stimulated inflammatory reactions in RAW264.7 cells and endotoxin shock in mice.

Abstract

Activated macrophages mediate inflammation, as they release nitric oxide and pro-inflammatory cytokines in various inflammatory diseases. Suppressing macrophage activation may alleviate inflammatory processes. Here, we report that (E)-3-(3,4-dihydroxy-2-methoxyphenyl)-1-(2,4-dihydroxyphenyl)prop-2-en-1-one (DDP), a novel licochalcone B derivative compound, inhibits inflammatory reactions in macrophages and protects mice from endotoxin shock. In vitro experiments showed that DDP suppressed the generation of nitric oxide and pro-inflammatory cytokines by suppressing the activation of nuclear factor-κB and activator protein-1 and simultaneously inhibited its upstream inflammatory signaling cascades in lipopolysaccharide in RAW264.7 cells. In an animal model, DDP protected BALB/c mice from lipopolysaccharide-induced endotoxin shock, possibly through inhibition of the production of inflammatory cytokines. DDP inhibited the production of inflammatory mediators and may be a potential target for treatment of various inflammatory diseases.

• Authors: Ju-Hyung Park, Jong-Gab Jun, Jin-Kyung Kim
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 224 Pg. 142-8 (Dec 05 2014) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 25451593 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• 3-(3,4-dihydroxy-2-methoxyphenyl)-1-(2,4-dihydroxyphenyl)prop-2-en-1-one
• Anti-Inflammatory Agents, Non-Steroidal
• Chalcones
• Interleukin-1beta
• Interleukin-6
• Lipopolysaccharides
• NF-kappa B
• Nitrites
• Protein Kinase Inhibitors
• Tumor Necrosis Factor-alpha
• interleukin-6, mouse
• lipopolysaccharide, Escherichia coli O111 B4
• Nitric Oxide
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinase 14
• licochalcone B

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
• Cell Line
• Chalcones (chemistry, pharmacology, therapeutic use)
• Interleukin-1beta (antagonists & inhibitors)
• Interleukin-6 (antagonists & inhibitors)
• JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors)
• Lipopolysaccharides (pharmacology)
• Mice
• Mitogen-Activated Protein Kinase 14 (antagonists & inhibitors)
• NF-kappa B (antagonists & inhibitors, genetics)
• Nitric Oxide (antagonists & inhibitors)
• Nitrites (analysis, metabolism)
• Protein Kinase Inhibitors (pharmacology)
• Shock, Septic (drug therapy, metabolism)
• Stereoisomerism
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)