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Arch Pharm Res. 2005 Mar;28(3):274-9.

Inhibition of interleukin-12 production in mouse macrophages via decreased nuclear factor-kappaB DNA binding activity by myricetin, a naturally occurring flavonoid.

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  • 1College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Korea.

Abstract

Pharmacological inhibition of interleukin-12 (IL-12) production may be a therapeutic strategy for preventing the development and progression of disease in experimental models of autoimmunity. In this study, the effects of myricetin, a naturally occurring flavonoid present in fruits, vegetables and medicinal herbs, on the production of IL-12 were investigated in mouse macrophages stimulated with lipopolysaccharide (LPS). Myricetin significantly inhibited the LPS-induced IL-12 production from both primary macrophages and the RAW264.7 monocytic cell-line in a dose-dependent manner. The effect of myricetin on IL-12 gene promoter activation was analyzed by transfecting RAW264.7 cells with IL-12 gene promoter/luciferase constructs. The repressive effect was mapped to a region in the IL-12 gene promoter containing a binding site for NF-kappaB. Furthermore, activation of macrophages by LPS resulted in markedly enhanced binding activity to the NF-kappaB site, which significantly decreased upon addition of myricetin, indicating that myricetin inhibited IL-12 production in LPS-activated macrophages via the down-regulation of NF-kappaB binding activity.

PMID:
15832812
[PubMed - indexed for MEDLINE]
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