title: Inhibitory effect of dihydroartemisinin against phorbol ester-induced cyclooxygenase-2 expression in macrophages.
abstract: 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.
authors: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 305-764, South Korea.
authors: Hyung Gyun
authors: HG
authors: Kim
authors: Ji Hye
authors: JH
authors: Yang
authors: Eun Hee
authors: EH
authors: Han
authors: Jae Ho
authors: JH
authors: Choi
authors: Tilak
authors: T
authors: Khanal
authors: Myung Ho
authors: MH
authors: Jeong
authors: Tae Cheon
authors: TC
authors: Jeong
authors: Hye Gwang
authors: HG
authors: Jeong
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D008156:Luciferases / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010703:Phorbol Esters / Q000009:adverse effects*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D037621:Artemisinins; D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D016328:NF-kappa B; D010703:Phorbol Esters; D010936:Plant Extracts; D018808:Transcription Factor AP-1; C039060:artenimol; D008156:Luciferases; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate