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

研究成果: 雜誌貢獻文章

45 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)263-269
頁數7
期刊Shock
32
發行號3
DOIs
出版狀態已發佈 - 九月 2009
對外發佈Yes

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

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