Inhibitory effects of [6]-gingerol on PMA-induced COX-2 expression and activation of NF-kappaB and p38 MAPK in mouse skin.
[6]-Gingerol, a major pungent ingredient of ginger (Zingiber officinale Roscoe, Zingiberaceae), has a wide array of pharmacologic effects. Previous studies have demonstrated that [6]-gingerol inhibits mouse skin tumor promotion and anchorage-independent growth of cultured mouse epidermal cells stimulated with epidermal growth factor. Cyclooxygenase-2 (COX-2), a key enzyme in the prostaglandin biosynthesis, has been recognized as a molecular target for many anti-inflammatory as well as chemopreventive agents. Topical application of [6]-gingerol inhibited phorbol 12-myristate 13-acetate -induced COX-2 expression. One of the essential transcription factors responsible for COX-2 induction is NF-kappaB. [6]-Gingerol suppressed NF-kappaB DNA binding activity in mouse skin. In addition, [6]-gingerol inhibited the phoshorylation of p38 mitogen-activated protein kinase which may account for its inactivation of NF-kappaB and suppression of COX-2 expression.
Kim
Sue Ok
SO
College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
Chun
Kyung-Soo
KS
Kundu
Joydeb Kumar
JK
Surh
Young-Joon
YJ
D000287:Administration, Topical; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D002396:Catechols; D051546:Cyclooxygenase 2; D004789:Enzyme Activation / Q000187:drug effects; D005233:Fatty Alcohols / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D020939:Zingiber officinale; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012867:Skin / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D016588:Anticarcinogenic Agents; D002396:Catechols; D005233:Fatty Alcohols; D016328:NF-kappa B; C007845:gingerol; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D048051:p38 Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate