Anti-inflammatory activity of ortho-trifluoromethoxy-substituted 4-piperidione-containing mono-carbonyl curcumin derivatives in vitro and in vivo
| Autor: | Wen-Wen Mu, Peng-Xiao Li, Guo-Yun Liu, Ziqing Wang, Jie Yang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Lipopolysaccharides
Curcumin medicine.drug_class Colon Anti-Inflammatory Agents Pharmaceutical Science 02 engineering and technology Pharmacology 030226 pharmacology & pharmacy Anti-inflammatory Nitric oxide 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine In vivo medicine Animals Colitis chemistry.chemical_classification Reactive oxygen species biology Dextran Sulfate 021001 nanoscience & nanotechnology medicine.disease Disease Models Animal chemistry Myeloperoxidase biology.protein Tumor necrosis factor alpha 0210 nano-technology |
| Zdroj: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 160 |
| ISSN: | 1879-0720 |
| Popis: | Curcumin was reported as an anti-inflammatory agent. However, curcumin's poor bioavailability limited its clinical utility. Here, thirty ortho-substituted mono-carbonyl curcumin derivatives, containing acetone, cyclopentanone, cyclohexanone or 4-piperidione (NH, N-methyl or N-acrylyl) moieties replacing β-diketone moiety of curcumin, were investigated for anti-inflammatory activity. Two active ortho-trifluoromethoxy-substituted 4-piperidione-containing derivatives 22 and 24 owned good cell uptake ability, and displayed excellent anti-inflammatory activity in both lipopolysaccharide-induced Raw264.7 macrophages and a dextran sulfate sodium (DSS)-induced mouse model of colitis. They inhibited the production of nitric oxide, reactive oxygen species, malonic dialdehyde and cyclooxygenase-2; and the expression of pro-inflammatory cytokines interleukin-1β, tumor necrosis factor-α and myeloperoxidase; the phosphorylation of mitogen-activated protein kinases; and the nucleus translocation of p65. What's more, 22 or 24 oral administered reduced the severity of clinical symptoms of ulcerative colitis (body weight and disease activity index), and reduced obviously DSS-induced colonic pathological damage (the colon length and histopathology analysis). These results suggested that ortho-trifluoromethoxy-substituted 4-piperidione-containing mono-carbonyl curcumin derivatives 22 and 24 were potential anti-inflammatory agents; and offered the important information for design and discovery of more potent anti-inflammatory drug candidates. |
| Databáze: | OpenAIRE |
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