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.
ASJC Scopus subject areas
- Critical Care and Intensive Care Medicine
- Emergency Medicine
Liu, Y. N., Pan, S. L., Liao, C. H., Huang, D. Y., Guh, J. H., Peng, C. Y., Chang, Y. L., & Teng, C. M. (2009). Evodiamine represses hypoxia-induced inflammatory proteins expression and hypoxia-inducible factor 1α accumulation in RAW264.7. Shock, 32(3), 263-269. https://doi.org/10.1097/SHK.0b013e31819940cb