Document Detail

Dioscoreanone suppresses LPS-induced nitric oxide production and inflammatory cytokine expression in RAW 264.7 macrophages by NF-κB and ERK1/2 signaling transduction.
MedLine Citation:
PMID:  22678775     Owner:  NLM     Status:  Publisher    
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-κB and ERK1/2 are demonstrated in RAW 264.7 cells. Through measurement with Griess reagent, dioscoreanone was found to reduce NO levels with an IC(50) value of 2.50 ± 0.64 µM, due to the significant suppression of LPS-induced iNOS mRNA expression, as well as IL-1β and IL-6 levels at a concentration of 6 µM. At the signal transduction level, using the pNFκB-Luciferase reporter system, dioscoreanone significantly inhibited NF-κB transcriptional activity, which resulted from the prevention of IκBα degradation. In addition, dioscoreanone in the range of 1.2-5 µM 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-1β and IL-6 were due to both the inhibition of NF-κB activation and the activation of ERK1/2 proteins. The activation of dioscoreanone may in turn inhibit the binding of NF-κB to pro-inflammatory gene promoters in LPS-induced RAW264.7 macrophage cells. J. Cell. Biochem. © 2012 Wiley Periodicals, Inc.
Arunporn Itharat; Poonsit Hiransai
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-7
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  -     ISSN:  1097-4644     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Department of Applied Thai Traditional Medicine, Faculty of Medicine, Thammasat University, Klongluang, Pathumtani, 12121, Thailand.
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