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Mechanism of HMGB1 release inhibition from RAW264.7 cells by oleanolic acid in Prunus mume Sieb. et Zucc.

Abstract：

: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.

journal_name

Int J Mol Med

journal_title

International journal of molecular medicine

authors

Kawahara K,Hashiguchi T,Masuda K,Saniabadi AR,Kikuchi K,Tancharoen S,Ito T,Miura N,Morimoto Y,Biswas KK,Nawa Y,Meng X,Oyama Y,Takenouchi K,Shrestha B,Sameshima H,Shimizu T,Adachi T,Adachi M,Maruyama I

doi

10.3892/ijmm_00000172

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

615-20

issue

5

eissn

1107-3756

issn

1791-244X

journal_volume

23

pub_type

杂志文章

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