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Title: Mechanism of HMGB1 release inhibition from RAW264.7 cells by oleanolic acid in Prunus mume Sieb. et Zucc
Authors: Ko Ichi Kawahara
Teruto Hashiguchi
Kazuo Masuda
Abbi R. Saniabadi
Kiyoshi Kikuchi
Salunya Tancharoen
Takashi Ito
Naoki Miura
Yoko Morimoto
Kamal K. Biswas
Yuko Nawa
Xiaojie Meng
Yoko Oyama
Kazunori Takenouchi
Binita Shrestha
Hisayo Sameshima
Toshiaki Shimizu
Taro Adachi
Masakazu Adachi
Ikuro Maruyama
Kagoshima University Faculty of Medicine
Showa Pharmaceutical College
Japan Immunoresearch Laboratories Company Limited
Mahidol University
Kagoshima University
AdaBio Co., Ltd.
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Jan-2009
Citation: International Journal of Molecular Medicine. Vol.23, No.5 (2009), 615-620
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)-α, 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.
ISSN: 1791244X
Appears in Collections:Scopus 2006-2010

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