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

• Published in: International immunopharmacology 2013-04, Vol.15 (4), p.743-751
• Main Authors: Xu, Jian, Jia, Yan-Yan, Chen, Shao-Rui, Ye, Jian-Tao, Bu, Xian-Zhang, Hu, Yun, Ma, Yun-Zi, Guo, Jin-Lei, Liu, Pei-Qing
• Format: Article
• Language: English
• Subjects: (E)-1-(4-ethoxyphenyl)-3-(4-nitrophenyl)-prop-2-en-1-one; 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; Inflammation; Interleukin-1beta - genetics; Interleukin-6 - genetics; Lipopolysaccharide; 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; NF-κB; Nitric Oxide Synthase Type II - genetics; Protein Transport; RAW 264.7 macrophages; Real-Time Polymerase Chain Reaction; Shock, Septic - prevention & control; Signal Transduction - drug effects; Survival Analysis; Tumor Necrosis Factor-alpha - genetics
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2013.02.024

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. •We have found a novel chalcone, ETH, which exhibits inhibitory effect on LPS induced inflammation.•ETH inhibits pro-inflammatory mediators expression on LPS stimulated RAW264.7 macrophages.•ETH suppresses the activation of NF-κB signaling pathway by LPS induction.