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KMID : 0578320130350040348
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Molecules and Cells
2013 Volume.35 No. 4 p.348 ~ p.354
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Acteoside Improves Survival in Cecal Ligation and Puncture-Induced Septic Mice via Blocking of High Mobility Group Box 1 Release
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Seo Eun-Sun
Oh Bo-Kang
Pak Jhang-Ho
Yim Soon-Ho
Sangilyandi Gurunathan
Kim Young-Pil
Lee Kyung-Jin
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Abstract
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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.
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KEYWORD
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acteoside, heme oxygenase 1, high-mobility group box 1, nrf2, p38, Raw264.7 cell, sepsis
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