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http://dx.doi.org/10.5352/JLS.2015.25.9.976

Effects of Achyranthoside C Dimethyl Ester on Heme Oxygenase-1 Expression and NO Production  

Bang, Soo Young (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
Song, Ji Su (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
Moon, Hyung-In (Department of Medicinal Biotechnology, College of Natural Resources and Life Science, Dong-A University)
Kim, YoungHee (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
Publication Information
Journal of Life Science / v.25, no.9, 2015 , pp. 976-983 More about this Journal
Abstract
Achyranthoside C dimethyl ester (ACDE) is an oleanolic acid glycoside from Achyranthes japonica which has been used in traditional medicine for the treatment of edema and arthritis. In this study, we investigated the anti-inflammatory effects of ACDE in RAW264.7 macrophages. ACDE significantly induced heme oxygenase-1 (HO-1) gene expression in RAW264.7 cells, while ACDE improved LPS-induced toxicity of cells. And ACDE induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. Further study demonstrated that ACDE-induced expression of HO-1 was inhibited by inhibitors of phosphatidylinositol 3-kinase (PI-3K) (LY294002), c-Jun kinase (JNK) (SP600125), extracellular signal regulated kinase (ERK) (PD98059) and p38 kinase (SB203580). Moreover, ACDE phosphorylated Akt, JNK, ERK, and p38 MAPK. In addition, ACDE inhibited LPS-induced NO secretion as well as inducible NO synthase (iNOS) expression in a dose-dependent manner. The inhibitory effects of ACDE on iNOS expression were abrogated by small interfering RNA (siRNA)-mediated knock-down of HO-1. Therefore, these results suggest that ACDE suppresses the production of pro-inflammatory mediator such as NO by inducing HO-1 expression via PI-3K/Akt/MAPK-Nrf2 signaling pathway. These findings could help us to understand the active principle included in the roots of A. japonica and the molecular mechanisms underlying anti-inflammatory action of ACDE.
Keywords
Achyranthoside C dimethyl ester; heme oxygenase-1; inducible nitric oxide synthase; NF-E2-related factor 2; nitric oxide;
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