Evodiamine represses hypoxia-induced inflammatory proteins expression and hypoxia-inducible factor 1α accumulation in RAW264.7

Yi Nan Liu, Shiow Lin Pan, Cho Hwa Liao, Der Yi Huang, Jih Hwa Guh, Chieh Yu Peng, Ya Ling Chang, Che Ming Teng

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Inflammation and low oxygen diffusion are recognized characteristics of cardiovascular diseases such as atherosclerosis. Evodiamine, extracted from the traditional Chinese herb, Evodia rutaecarpa, is a bioactive anti-inflammatory alkaloid. The objective of this study was to investigate whether evodiamine could repress hypoxia-induced inflammatory response. We showed that evodiamine repressed not only COX-2 and iNOS expression but also prostaglandin E2 release in a concentration-dependent manner under hypoxic conditions. Furthermore, our studies indicated that COX-2 mRNA was inhibited by evodiamine, implying that transcriptional activity is involved in the mechanistic pathway. It is striking that hypoxia-inducible factor 1α (HIF-1α) inhibitor, camptothecin, suppressed hypoxia-induced COX-2 expression rather than pyrrolidine dithiocarbamate, a nuclear factor κB inhibitor. In addition, our studies have confirmed that evodiamine inhibited HIF-1α, which accounted for the transcriptional activity of COX-2, rather than nuclear factor κB in RAW264.7 cells. Finally, evodiamine did not affect either the level of HIF-1α mRNA or the degradation rate of HIF-1α protein, but it regulated the translational process of HIF-1α. We found that hypoxia-evoked phosphorylation of Akt and p70S6K was blocked after evodiamine treatment, in addition to the inhibition of phosphorylation of 4E-BP. These results suggest that the mechanism of repression of hypoxia-induced COX-2 expression by evodiamine is through the inhibition of HIF-1α at the translational level and is primarily mediated via dephosphorylation of Akt and p70S6K. Therefore, evodiamine could be an effective therapeutic agent against inflammatory diseases involving hypoxia.

Original languageEnglish
Pages (from-to)263-269
Number of pages7
JournalShock
Volume32
Issue number3
DOIs
Publication statusPublished - Sep 2009
Externally publishedYes

Fingerprint

Hypoxia-Inducible Factor 1
Proteins
70-kDa Ribosomal Protein S6 Kinases
Evodia
Phosphorylation
evodiamine
Hypoxia
Camptothecin
RNA Stability
Dinoprostone
Alkaloids
Atherosclerosis
Anti-Inflammatory Agents
Cardiovascular Diseases
Oxygen
Inflammation
Messenger RNA

Keywords

  • Macrophage
  • p70S6K
  • Translation

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Evodiamine represses hypoxia-induced inflammatory proteins expression and hypoxia-inducible factor 1α accumulation in RAW264.7. / Liu, Yi Nan; Pan, Shiow Lin; Liao, Cho Hwa; Huang, Der Yi; Guh, Jih Hwa; Peng, Chieh Yu; Chang, Ya Ling; Teng, Che Ming.

In: Shock, Vol. 32, No. 3, 09.2009, p. 263-269.

Research output: Contribution to journalArticle

Liu, Yi Nan ; Pan, Shiow Lin ; Liao, Cho Hwa ; Huang, Der Yi ; Guh, Jih Hwa ; Peng, Chieh Yu ; Chang, Ya Ling ; Teng, Che Ming. / Evodiamine represses hypoxia-induced inflammatory proteins expression and hypoxia-inducible factor 1α accumulation in RAW264.7. In: Shock. 2009 ; Vol. 32, No. 3. pp. 263-269.
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