Linked Life Data

19027002

Source:http://linkedlifedata.com/resource/pubmed/id/19027002

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2009-1-12
pubmed:abstractText
We investigated the effect of desmethylanhydroicaritin (DMAI), a major compound of the Chinese herbal medicine Epimedium, on inflammatory gene expression and the NF-kappaB signaling pathway. We found that DMAI suppressed the expression of NF-kappaB-responsive genes, such as inducible nitric oxide synthase, cyclooxygenase-2, interleukin-1beta, and tumor necrosis factor-alpha, in lipopolysaccharide (LPS)-stimulated macrophages and endotoxemic mice as well as protected mice against LPS-induced lethality. DMAI inhibited NF-kappaB activation through the inhibition of IkappaB kinase (IKK) activation, IkappaB phosphorylation and degradation, and NF-kappaB nuclear translocation in LPS-stimulated macrophages. This compound inhibited in vitro and in vivo LPS-induced phosphatidylinositol 3-kinase (PI3K) activation, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) oxidation, and Akt phosphorylation, which are upstream modulators of IKK activation. Moreover, treatment with DMAI was not observed to affect the interaction between the Toll-like receptor 4, MyD88, and TRAF6 as well as mitogen-activated protein kinase activation. DMAI also suppressed intracellular H(2)O(2) accumulation, hydroxyl radical production, and glutathione oxidation without affecting superoxide generation and accumulation by NADPH oxidase. Moreover, DMAI inhibited redox-sensitive activation of the PI3K/PTEN/Akt pathway and NF-kappaB activation in macrophages treated with H(2)O(2). These results indicate that DMAI negatively regulates canonical NF-kappaB-regulated inflammatory gene expression by functioning as an inhibitor of the NF-kappaB pathway through the suppression of redox-based PI3K activation and PTEN inactivation and therefore can be considered as a potential drug for inflammatory diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1879-0712
pubmed:author
pubmed:issnType
Electronic
pubmed:day
14
pubmed:volume
602
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
422-31
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:19027002-Animals, pubmed-meshheading:19027002-Cell Line, pubmed-meshheading:19027002-Endotoxemia, pubmed-meshheading:19027002-Enzyme Activation, pubmed-meshheading:19027002-Female, pubmed-meshheading:19027002-Flavones, pubmed-meshheading:19027002-Gene Expression Regulation, pubmed-meshheading:19027002-Hydrogen Peroxide, pubmed-meshheading:19027002-Inflammation, pubmed-meshheading:19027002-Intracellular Space, pubmed-meshheading:19027002-Lipopolysaccharides, pubmed-meshheading:19027002-Macrophages, Peritoneal, pubmed-meshheading:19027002-Mice, pubmed-meshheading:19027002-NF-kappa B, pubmed-meshheading:19027002-Oxidation-Reduction, pubmed-meshheading:19027002-PTEN Phosphohydrolase, pubmed-meshheading:19027002-Phosphatidylinositol 3-Kinases, pubmed-meshheading:19027002-Proto-Oncogene Proteins c-akt, pubmed-meshheading:19027002-Signal Transduction
pubmed:year
2009
pubmed:articleTitle
Desmethylanhydroicaritin inhibits NF-kappaB-regulated inflammatory gene expression by modulating the redox-sensitive PI3K/PTEN/Akt pathway.
pubmed:affiliation
Vascular System Research Center, Kangwon National University, Chuncheon, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't