Geranyl flavones have been studied as compounds that potentially can be developed as anti-inflammatory agents. A series of natural geranylated flavanones was isolated from Paulownia tomentosa fruits, and these compounds were studied for their anti-inflammatory activity and possible mechanism of action. Two new compounds were characterized [paulownione C (17) and tomentodiplacone O (20)], and all of the isolated derivatives were assayed for their ability to inhibit cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX). The compounds tested showed variable degrees of activity, with several of them showing activity comparable to or greater than the standards used in COX-1, COX-2, and 5-LOX assays. However, only the compound tomentodiplacone O (20) showed more selectivity against COX-2 versus COX-1 when compared with ibuprofen. The ability of the test compounds to interact with the above-mentioned enzymes was supported by docking studies, which revealed the possible incorporation of selected test substances into the active sites of these enzymes. Furthermore, one of the COX/LOX dual inhibitors, diplacone (14) (a major geranylated flavanone of P. tomentosa), was studied in vitro to obtain a proteomic overview of its effect on inflammation in LPS-treated THP-1 macrophages, supporting its previously observed anti-inflammatory activity and revealing the mechanism of its anti-inflammatory effect.
- MeSH
- antiflogistika chemie izolace a purifikace farmakologie MeSH
- arachidonát-5-lipoxygenasa metabolismus MeSH
- cyklooxygenasa 1 metabolismus MeSH
- cyklooxygenasa 2 metabolismus MeSH
- flavonoidy chemie izolace a purifikace farmakologie MeSH
- inhibitory cyklooxygenasy 2 chemie izolace a purifikace farmakologie MeSH
- inhibitory lipoxygenas chemie izolace a purifikace farmakologie MeSH
- Magnoliopsida chemie MeSH
- molekulární struktura MeSH
- ovoce chemie MeSH
- proteomika * MeSH
- Publikační typ
- časopisecké články MeSH
Cudraflavone B (1) is a prenylated flavonoid found in large amounts in the roots of Morus alba, a plant used as a herbal remedy for its reputed anti-inflammatory properties. The present study shows that this compound causes a significant inhibition of inflammatory mediators in selected in vitro models. Thus, 1 was identified as a potent inhibitor of tumor necrosis factor α (TNFα) gene expression and secretion by blocking the translocation of nuclear factor κB (NF-κB) from the cytoplasm to the nucleus in macrophages derived from a THP-1 human monocyte cell line. The NF-κB activity reduction resulted in the inhibition of cyclooxygenase 2 (COX-2) gene expression. Compound 1 acts as a COX-2 and COX-1 inhibitor with higher selectivity toward COX-2 than indomethacin. Pretreatment of cells by 1 shifted the peak in an regulatory gene zinc-finger protein 36 (ZFP36) expression assay. This natural product has noticeable anti-inflammatory properties, suggesting that 1 potentially could be used for development as a nonsteroidal anti-inflammatory drug lead.
- MeSH
- aktiny účinky léků MeSH
- antiflogistika nesteroidní chemie izolace a purifikace farmakologie MeSH
- cyklooxygenasa 1 účinky léků MeSH
- flavonoidy chemie izolace a purifikace farmakologie MeSH
- inhibitory cyklooxygenasy 2 chemie izolace a purifikace farmakologie MeSH
- kořeny rostlin chemie MeSH
- lidé MeSH
- makrofágy účinky léků MeSH
- molekulární struktura MeSH
- Morus chemie MeSH
- NF-kappa B antagonisté a inhibitory MeSH
- TNF-alfa antagonisté a inhibitory genetika MeSH
- tristetraprolin účinky léků genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
