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Anti-inflammatory mechanisms of isoflavone metabolites in lipopolysaccharide-stimulated microglial cells

Title
Anti-inflammatory mechanisms of isoflavone metabolites in lipopolysaccharide-stimulated microglial cells
Authors
Park J.-S.Woo M.-S.Kim D.-H.Hyun J.-W.Kim W.-K.Lee J.-C.Kim H.-S.
Ewha Authors
김희선박진선
SCOPUS Author ID
김희선scopus; 박진선scopus
Issue Date
2007
Journal Title
Journal of Pharmacology and Experimental Therapeutics
ISSN
0022-3565JCR Link
Citation
vol. 320, no. 3, pp. 1237 - 1245
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
The microglial activation plays an important role in neurodegenerative diseases by producing several proinflammatory cytokines and nitric oxide (NO). We found that three types of isoflavones and their metabolites that are transformed by the human intestinal microflora suppress lipopolysaccharide (LPS)-induced release of NO and tumor necrosis factor (TNF)-α in primary cultured microglia and BV2 microglial cell lines. The inhibitory effect of the isoflavone metabolites (aglycon form) was more potent than that of isoflavones (glycoside form). The RNase protection assay showed that the isoflavone metabolites regulated inducible nitric oxide synthase (iNOS) and the cytokines at either the transcriptional or post-transcriptional level. A further molecular mechanism study was performed for irisolidone, a metabolite of kakkalide, which had the most potent anti-inflammatory effect among the six isoflavones tested. Irisolidone significantly inhibited the DNA binding and transcriptional activity of nuclear factor (NF)-κB and activator protein-1. Moreover, it repressed the LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation without affecting the activity of c-Jun N-terminal kinase or p38 mitogen-activated protein kinase. The level of NF-κB inhibition by irisolidone correlated with the level of iNOS, TNF-α, and interleukin (IL)-1β suppression in LPS-stimulated microglia, whereas the level of ERK inhibition correlated with the level of TNF-α and IL-1β repression. Overall, the repression of proinflammatory cytokines and iNOS gene expression in activated microglia by isoflavones such as irisolidone might have therapeutic potential for various neurodegenerative diseases including ischemic cerebral disease. Copyright © 2007 by The American Society for Pharmacology and Experimental Therapeutics.
DOI
10.1124/jpet.106.114322
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
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