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KMID : 0613820130230060736
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Journal of Life Science
2013 Volume.23 No. 6 p.736 ~ p.742
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Anti-inflammatory Effect of Achyranthoside E Dimethyl Ester in LPS-stimulated RAW 264.7 Cells
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Bang Soo-Young
Kim Ji-Hee
Moon Hyung-In
Kim Young-Hee
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Abstract
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Achyranthoside E dimethyl ester (AEDE) is an oleanolic acid glycoside from Achyranthes japonica. In this study, we investigated the effects of AEDE on nitric oxide (NO) production and underlying molecular mechanisms in lipopolysaccharide (LPS)-stimulated macrophages. AEDE inhibited LPS-induced NO secretion as well as inducible NO synthase (iNOS) expression, without affecting cell viability. Further study demonstrated that AEDE induced heme oxygenase-1 (HO-1) gene expression. In addition, the inhibitory effects of AEDE on iNOS expression were abrogated by small interfering RNA-mediated knock-down of HO-1. Moreover, AEDE induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. AEDE-induced expression of HO-1 was inhibited by inhibitors of phosphatidylinositol 3-kinase (PI-3K) and extracellular signal regulated kinase (ERK1/2). AEDE phosphorylated Akt and ERK1/2 as well. Therefore, these results suggest that AEDE suppresses the production of pro-inflammatory mediator such as NO by inducing HO-1 expression via PI-3K/Akt/ERK-Nrf2 signaling. These findings provide the scientific rationale for anti-inflammatory therapeutic use of AEDE.
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KEYWORD
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Achyranthoside E dimethyl ester, heme oxygenase-1, inducible nitric oxide synthase, NF-E2-related factor 2, nitric oxide
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