Linked Life Data

17320913

Source:http://linkedlifedata.com/resource/pubmed/id/17320913

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2007-3-13
pubmed:abstractText
Chalcone, an alpha,beta-unsaturated flavonoid, possesses anti-inflammatory properties. In our present study, we have demonstrated chalcone inhibited IL-6- and LPS-induced ICAM-1 gene expression. In adhesion assay, chalcone reduced the LPS-induced adhesion of THP-1 cells to endothelial cells (ECs). Chalcone was found to abrogate the activation of STAT3 and NF-kappaB in a dose- and time-dependent manner, in IL-6- and LPS-treated ECs. Other flavonoids, quercetin and cyanidin, which lack alpha,beta-unsaturated carbonyl group, showed weaker or no inhibitory effect on both IL-6-induced STAT3 phosphorylation and LPS-induced p65 translocation. However, the electrophilic compounds curcumin and crotonaldehyde, which also contain an alpha,beta-unsaturated carbonyl moiety, mimic the inhibitory effects of chalcone with different efficiencies. In addition, N-acetyl-L-cysteine (NAC) could reverse the inhibition of STAT3 phosphorylation when preincubated with chalcone. The use of buthionine sulfoximine (BSO) to decrease intracellular GSH levels further enhanced the effects of chalcone. On the other hand, in ECs treated with BSO only no abrogation of IL-6-induced STAT3 phosphorylation was observed. We also found that chalcone could reduce the GSH level in vitro. Furthermore, the cellular GSH levels were rapidly reduced after 25 microM chalcone treatment. Following 6 h exposure, however, chalcone treatment rescued the GSH levels in ECs, coincident with the inhibition of STAT3 and NF-kappaB activation. In contrast, chalcone induced expression of thioredoxin reductase and heme-oxygenase genes after prolonged treatment. Furthermore, chalcone upregulated the levels of the transcription factor Nrf2 in nuclear extracts and increased antioxidant response element (ARE)-luciferase activity and thioredoxin reductase promoter activity. Hence, our present findings indicate that chalcone suppresses both IL-6- and LPS-induced signaling pathways through the thiol-dependent intracellular redox state. In addition, chalcone may provide distinct cytoprotective effects at different durations of pretreatment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0024-3205
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
80
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1420-30
pubmed:meshHeading
pubmed-meshheading:17320913-Animals, pubmed-meshheading:17320913-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:17320913-Blotting, Northern, pubmed-meshheading:17320913-Blotting, Western, pubmed-meshheading:17320913-Cattle, pubmed-meshheading:17320913-Cell Adhesion Molecules, pubmed-meshheading:17320913-Cell Nucleus, pubmed-meshheading:17320913-Cell Survival, pubmed-meshheading:17320913-Cells, Cultured, pubmed-meshheading:17320913-Chalcone, pubmed-meshheading:17320913-Coculture Techniques, pubmed-meshheading:17320913-Endothelial Cells, pubmed-meshheading:17320913-Glutathione, pubmed-meshheading:17320913-Interleukin-6, pubmed-meshheading:17320913-Lipopolysaccharides, pubmed-meshheading:17320913-Luciferases, pubmed-meshheading:17320913-Monocytes, pubmed-meshheading:17320913-NF-kappa B, pubmed-meshheading:17320913-Plasmids, pubmed-meshheading:17320913-RNA, pubmed-meshheading:17320913-STAT3 Transcription Factor, pubmed-meshheading:17320913-Transfection
pubmed:year
2007
pubmed:articleTitle
Chalcone inhibits the activation of NF-kappaB and STAT3 in endothelial cells via endogenous electrophile.
pubmed:affiliation
Institute of Biotechnology, National Chiayi University, Chiayi, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't