title: Acteoside improves survival in cecal ligation and puncture-induced septic mice via blocking of high mobility group box 1 release.
abstract: Acteoside, an active phenylethanoid glycoside, has been used traditionally as an anti-inflammatory agent. The molecular mechanism by which acteoside reduces inflammation was investigated in lipopolysaccharide (LPS)-induced Raw264.7 cells and in a mouse model of cecal ligation and puncture (CLP)-induced sepsis. In vitro, acteoside inhibits high mobility group box 1 (HMGB1) release and iNOS/NO production and induces heme oxygenase-1 (HO-1) expression in a concentration-dependent manner, while HO-1 siRNA antagonizes the inhibition of HMGB1 and NO. The effect of acteoside is inhibited by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 and Nfr2 siRNA, indicating that acteoside induces HO-1 via p38 MAPK and NF-E2-related factor 2 (Nrf2). In vivo, acteoside increases survival and decreases serum and lung HMGB1 levels in CLP-induced sepsis. Overall, these results that acteoside reduces HMGB1 release and may be beneficial for the treatment of sepsis.
authors.affiliation: Department of Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Korea.
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Seo
authors.forename: Bo Kang
authors.initials: BK
authors.lastname: Oh
authors.forename: Jhang Ho
authors.initials: JH
authors.lastname: Pak
authors.forename: Soon-Ho
authors.initials: SH
authors.lastname: Yim
authors.forename: Sangilyandi
authors.initials: S
authors.lastname: Gurunathan
authors.forename: Young-Pil
authors.initials: YP
authors.lastname: Kim
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D002432:Cecum / Q000187:drug effects* / Q000601:surgery*; D005960:Glucosides / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008026:Ligation / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010636:Phenols / Q000494:pharmacology*; D018805:Sepsis / Q000209:etiology* / Q000276:immunology / Q000401:mortality; D059808:Polyphenols
chemical_list: D005960:Glucosides; D024243:HMGB1 Protein; D051547:Heme Oxygenase-1; D010636:Phenols; C058956:acteoside; D059808:Polyphenols
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