Linked Life Data

19360320

Source:http://linkedlifedata.com/resource/pubmed/id/19360320

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-4-10
pubmed:abstractText
High mobility group box-1 protein (HMGB1), primarily from the nucleus, is released into the extracellular milieu either passively from necrotic cells or actively through secretion by monocytes/macrophages. Extracellular HMGB1 acts as a potent inflammatory agent by promoting the release of cytokines such as tumor necrosis factor (TNF)-alpha, has procoagulant activity, and is involved in death due to sepsis. Accordingly, HMGB1 is an appropriate therapeutic target. In this study, we found that an extract of Prunus mume Sieb. et Zucc. (Ume) fruit (Ume extract), an abundant source of triterpenoids, strongly inhibited HMGB1 release from lipopolysaccharide (LPS)-stimulated macrophage-like RAW264.7 cells. The inhibitory effect on HMGB1 release was enhanced by authentic oleanolic acid (OA), a naturally occurring triterpenoid. Similarly, the HMGB1 release inhibitor in Ume extract was found to be OA. Regarding the mechanisms of the inhibition of HMGB1 release, the OA or Ume extract was found to activate the transcription factor Nrf2, which binds to the antioxidative responsive element, and subsequently the heme oxygenase (HO)-1 protein was induced, indicating that the inhibition of HMGB1 release from LPS-stimulated RAW264.7 cells was mediated via the Nrf2/HO-1 system; an essentially antioxidant effect. These results suggested that natural sources of triterpenoids warrant further evaluation as 'rescue' therapeutics for sepsis and other potentially fatal systemic inflammatory disorders.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1107-3756
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
615-20
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Mechanism of HMGB1 release inhibition from RAW264.7 cells by oleanolic acid in Prunus mume Sieb. et Zucc.
pubmed:affiliation
Department of Laboratory and Vascular Medicine Cardiovascular and Respiratory Disorders Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't