Kaufmann, Kai B. and Gothwal, Monika and Schallner, Nils and Ulbrich, Felix and Ruecker, Hannelore and Amslinger, Sabine and Goebel, Ulrich (2016) The anti-inflammatory effects of E-alpha-(p-methoxypheny1)-2 ',3,4,4 '-tetramethoxychalcone are mediated via HO-1 induction. INTERNATIONAL IMMUNOPHARMACOLOGY, 35. pp. 99-110. ISSN 1567-5769, 1878-1705
Full text not available from this repository. (Request a copy)Abstract
Inflammation plays a central role in the pathophysiology of many diseases. The inducible enzyme heme oxygenase-1 (HO-1) protects cells against inflammation and can be induced by electrophilic compounds like the chalcones (1,3-diphenylprop-2-enones) from the class of alpha,beta-unsaturated carbonyl compounds. We hypothesized that the synthetic chalcone E-alpha-(p-methoxyphenyl)-2',3,4,4'-tetramethoxychalcone (E-alpha-p-OMe-C6H4-TMC) exerts anti-inflammatory effects in RAW264.7, Jurkat lymphocytes and HK-2 cells via HO-1 induction. RAW264.7 cells were treated with lipopolysaccharide prior to E-alpha-p-OMe-C6H4-TMC treatment. Subsequently, HO-1 protein induction and activity were analyzed, as well as expression of pro- and anti-inflammatory mediators, transcription factors and mitogen-activated protein kinases to evaluate the possible molecular mechanism. These results were confirmed in human cell lines (Jurkat T-lymphocytes and HK-2 epithelial cells). We found that the E-alpha-p-OMe-C6H4-TMC exerts significant anti-inflammatory effects in a dose dependent manner, showing no toxic effects in LPS-treated RAW264.7 macrophages. E-alpha-p-OMe-C6H4-TMC induced HO-1 and SOD-1 protein expression and HO-1 enzyme activity, reduced the upregulation of COX-2 and 1NOS, while inducing the translocation of Nrf2. NF-kappa B activity was attenuated following E-alpha-p-OMe-C6H4-TMC treatment accompanied by the downregulation of proinflammatory cytokines IL-1 beta, IL-6 and MCP-1. Pretreatment with E-alpha-p-OMe-C6H4-TMC revealed significant changes in phosphorylation of ERK and p38, but not JNK. These anti-inflammatory effects of E-alpha-p-OMe-C6H4-TMC were approved in Jurkat and HK-2 cells, furthermore revealing a downregulation of IL-8 and IL-10. In conclusion, it is tempting to speculate about E-alpha-p-OMe-C6H4-TMC as a new and non-toxic agent, inducing HO-1 in cells. This opens up new opportunities regarding the development of therapeutic agents using beneficial effects of HO-1 and its products. (C) 2016 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEME OXYGENASE-1 INDUCTION; NITRIC-OXIDE PRODUCTION; NF-KAPPA-B; CARBON-MONOXIDE; COBALT-PROTOPORPHYRIN; ACTIVATOR PROTEIN-1; MURINE MACROPHAGES; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; GENE-EXPRESSION; Chalcone; HO-1; Inflammation; Nrf2; NF-kappa B; MAPK |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Organische Chemie > Arbeitskreis Dr. Sabine Amslinger |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Mar 2019 13:48 |
| Last Modified: | 25 Mar 2019 13:48 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2890 |
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