Inhibiting NF-κB-Mediated Inflammation by Catechol-Type Diphenylbutadiene via an Intracellular Copper- and Iron-Dependent Pro-Oxidative Role
| Autor: | Yu-Ting Du, Bo Zhou, Ya-Long Zheng, Fang Dai |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0106 biological sciences
Chemistry 010401 analytical chemistry Inflammation General Chemistry Oxidative phosphorylation IκB kinase 01 natural sciences Dithiothreitol 0104 chemical sciences Neocuproine Deferoxamine chemistry.chemical_compound Biochemistry medicine Phosphorylation medicine.symptom General Agricultural and Biological Sciences Intracellular 010606 plant biology & botany medicine.drug |
| Zdroj: | Journal of Agricultural and Food Chemistry. 68:10029-10035 |
| ISSN: | 1520-5118 0021-8561 |
| DOI: | 10.1021/acs.jafc.0c04399 |
| Popis: | Chronic inflammation mediated by nuclear factor-κB (NF-κB) plays a crucial role in the development of cancer. As part of our continuous efforts placed on investigating anticancer mechanisms of dietary catechols, we further applied catechol-type diphenylbutadiene (3,4-DHB) as a model molecule to probe whether it inhibits inflammation by its pro-oxidative role. Employing lipopolysaccharide-stimulated RAW264.7 cells as a model of inflammation, we validated that benefiting from its catechol moiety, 3,4-DHB inhibited significantly the LPS-induced formation of NO (11.48 ± 0.39 μM) compared with the only LPS-stimulated group (31.8 ± 1.78 μM) with an inhibitory rate of 64% at 5 μM, expression of iNOS and COX-2 proteins, phosphorylation of IkB kinase and IkBα, and nuclear translocation of NF-κB. Noticeably, its inhibitory activity against the NF-κB-mediated inflammation can be obviously revised by pretreatment of the cells with dithiothreitol (a quencher of both electrophilic o-quinone and ROS), neocuproine (a specific chelating agent for copper ions), and deferoxamine (a specific chelating agent for iron ions). The above results support that depending on intracellular copper and iron ions, 3,4-DHB, a pro-electrophile, can be converted into its corresponding o-quinone electrophile together with the generation of ROS, a pro-oxidative event that mediates its inhibitory activity against NF-κB signaling and inflammation. The copper- and iron-dependent inhibition against inflammation supports that dietary catechols are probably pro-oxidative anti-inflammatory agents. |
| Databáze: | OpenAIRE |
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