Induction of cyclooxygenase-2 by ginsenoside Rd via activation of CCAAT-enhancer binding proteins and cyclic AMP response binding protein.
Panax ginseng is a widely used herbal medicine in East Asia and is reported to have a variety of pharmacological effects against cardiovascular diseases and cancers. Here we show a unique effect of ginsenoside Rd (Rd) on cyclooxygenase-2 (COX-2) expression in RAW264.7 macrophages. Rd (100 microg/ml), but not other ginsenosides induced COX-2 and increased prostaglandin E(2) production. Gel shift and Western blot analyses using nuclear fractions revealed that Rd increased both the DNA binding of and the nuclear levels of CCAAT/enhancer binding protein (C/EBP)alpha/beta and cyclic AMP response element binding protein (CREB), but not of p65, in RAW264.7 cells. Moreover, Rd increased the luciferase reporter gene activity in cells transfected with a 574-bp mouse COX-2 promoter construct. Site-specific mutation analyses confirmed that Rd-mediated transcriptional activation of COX-2 gene was regulated by C/EBP and CREB. These results provide evidence that Rd activated C/EBP and CREB, and that the activation of C/EBP and CREB appears to be essential for induction of COX-2 in RAW264.7 cells.
Jeong
Hye Gwang
HG
BK21 Project Team, College of Pharmacy, Chosun University, Seosuk-dong, Dong-gu, Gwangju 501-759, South Korea.
Pokharel
Yuba Raj
YR
Han
Eun Hee
EH
Kang
Keon Wook
KW
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D036145:Ginsenosides / Q000008:administration & dosage*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology
D022762:CCAAT-Enhancer-Binding Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D036145:Ginsenosides; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C049863:ginsenoside Rd