Acteoside improves survival in cecal ligation and puncture-induced septic mice via blocking of high mobility group box 1 release |
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Authors: | Eun Sun Seo Bo Kang Oh Jhang Ho Pak Soon-Ho Yim Sangilyandi Gurunathan Young-Pil Kim Kyung Jin Lee |
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Affiliation: | 121. Department of Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 138-736, Korea 221. Department of Optometry, Dong Shin University, Naju, 520-714, Korea 321. Department of Animal Biotechnology, Konkuk University, Seoul, 143-701, Korea 421. Department of Life Science, Hanyang University, Seoul, 133-791, Korea
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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. |
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Keywords: | acteoside heme oxygenase 1 high-mobility group box 1 nrf2 p38 Raw264.7 cell sepsis |
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