期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 113, 期 11, 页码 3427-3435出版社
WILEY-BLACKWELL
DOI: 10.1002/jcb.24219
关键词
PHENANTHRAQUINONE; Dioscorea membranacea; NITRIC OXIDE PRODUCTION; INFLAMMATORY CYTOKINES; RAW 264; 7 CELLS
资金
- National Research Council of Thailand, Bangkok, Thailand
- National Research University Project of Thailand Office of Higher Education Commission under Thammasat University, Bangkok, Thailand
- Walailak University, Thasala, Nakhon Si Thammarat, Thailand
Dioscoreanone, a 1,4-phenanthraquinone isolated from an ethanolic extract of the rhizome of Dioscorea membranacea, Pierre ex Prain & Burkill, a plant which has been used to treat inflammation and cancer in Thai Traditional Medicine. In this study, the mechanisms of dioscoreanone on LPS-induced NO production and cytokine expression through the activation of NF-?B and ERK1/2 are demonstrated in RAW 264.7 cells. Through measurement with Griess reagent, dioscoreanone was found to reduce NO levels with an IC50 value of 2.50 +/- 0.64 mu M, due to the significant suppression of LPS-induced iNOS mRNA expression, as well as IL-1 beta and IL-6 levels at a concentration of 6 mu M. At the signal transduction level, using the pNF?B-Luciferase reporter system, dioscoreanone significantly inhibited NF-?B transcriptional activity, which resulted from the prevention of I?Ba degradation. In addition, dioscoreanone in the range of 1.25 mu M significantly enhanced LPS-induced ERK1/2 activation and dioscoreanone alone induced the activation of ERK1/2 proteins in a concentration- and time-dependent response. The activation of ERK1/2 proteins by dioscoreanone was due to both an arylating reaction, which was suppressed by N-acetyl cysteine, and a redox cycling reaction of NQOR, which was inhibited by dicoumarol. In conclusion, the mechanisms of dioscoreanone on the inhibition of NO production and mRNA expression of iNOS, IL-1 beta, and IL-6 were due to both the inhibition of NF-?B activation and the activation of ERK1/2 proteins. The activation of dioscoreanone may in turn inhibit the binding of NF-?B to pro-inflammatory gene promoters in LPS-induced RAW264.7 macrophage cells. J. Cell. Biochem. 113: 34273435, 2012. (C) 2012 Wiley Periodicals, Inc.
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