Inhibitory effect of dihydroartemisinin against phorbol ester-induced cyclooxygenase-2 expression in macrophages

Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin isolated from the traditional Chinese herb Artemisia annua L., has recently been shown to possess antitumor activity in various cancer cells. However, the effect of anti-inflammatory potentials of DHA in murine macrophage RAW 264.7 cells has not been studied. The present study investigated the effect of COX-2 and molecular mechanisms by DHA in PMA stimulated RAW 264.7 cells. DHA dose-dependently decreased PMA-induced COX-2 expression and PGE2 production, as well as COX-2 promoter-driven luciferase activity. Additionally, DHA decreased luciferase activity of COX-2 regulation-related transcription factors including NF-κB, AP-1, C/EBP and CREB. DHA also remarkably reduced PMA-induced p65, C/EBPβ, c-jun and CREB nuclear translocation. Furthermore, DHA evidently inhibited PMA-induced phosphorylation of AKT and the MAP Kinases, such as ERK, JNK and p38. Taken together, our data indicated that DHA effectively attenuates COX-2 production via down-regulation of AKT and MAPK pathway, revealing partial molecular basis for the anti-inflammatory properties of DHA.