| Dietary flavones and flavonoles are inhibitors of poly(ADP-ribose)polymerase-1 in pulmonary epithelial cells. | |
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MedLine Citation:
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PMID: 17884996 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1), which was initially known to be highly activated by oxidative stress-induced DNA strand breaks, has been shown to be involved in the pathophysiology of acute and chronic inflammatory diseases. PARP-1 deficiency in mice led to the discovery of its coactivating function in the nuclear factor-kappa B-mediated gene expression and in addition, pharmaceutical inhibition of PARP-1 was shown to reduce the production of inflammatory mediators. In this study, the in vitro PARP-1-inhibiting effect of various flavonoids was investigated. The flavonoids myricetin, tricetin, gossypetin, delphinidin, quercetin, and fisetin were identified as significant inhibitors of the purified enzyme. Further evaluation of these compounds in N-methyl-N'-nitro-N-nitrosoguanidine-treated human pulmonary epithelial cells showed that the formation of the poly(ADP-ribose) polymers, as well as the decreased NAD(+) levels, was reduced by quercetin, fisetin, and tricetin. Finally, IL-8 production of LPS-stimulated human pulmonary epithelial cells could be significantly reduced by these flavonoids. The results of this study indicate that specific flavonoids have PARP-1-inhibiting activity in addition to the earlier described antioxidant effects. PARP-1 inhibition and preservation of cellular NAD(+) and energy production could play a role in the antiinflammatory activity of these specific flavonoids. In addition, these results indicate additional mechanisms by which flavonoids can exert antiinflammatory activity. Furthermore, these results indicate possibilities to use food-derived flavonoids in the treatment of chronic inflammatory diseases. |
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Authors:
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Liesbeth Geraets; Harald J J Moonen; Karen Brauers; Emiel F M Wouters; Aalt Bast; Geja J Hageman |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of nutrition Volume: 137 ISSN: 0022-3166 ISO Abbreviation: J. Nutr. Publication Date: 2007 Oct |
Date Detail:
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Created Date: 2007-09-21 Completed Date: 2007-11-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0404243 Medline TA: J Nutr Country: United States |
Other Details:
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Languages: eng Pagination: 2190-5 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Toxicology, Maastricht University, 6200 MD Maastricht, The Netherlands. l.geraets@farmaco.unimaas.nl |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line, Tumor Diet Flavones / pharmacology* Flavonols / pharmacology* Humans Interleukin-8 / metabolism Lung / cytology, metabolism Methylnitronitrosoguanidine / pharmacology NAD / metabolism NF-kappa B / metabolism Poly(ADP-ribose) Polymerases / antagonists & inhibitors* Respiratory Mucosa / cytology*, drug effects*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Flavones; 0/Flavonols; 0/Interleukin-8; 0/NF-kappa B; 53-84-9/NAD; 70-25-7/Methylnitronitrosoguanidine; EC 2.4.2.30/PARP1 protein, human; EC 2.4.2.30/Poly(ADP-ribose) Polymerases |
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