Inhibitory effects of [6]-gingerol on PMA-induced COX-2 expression and activation of NF-kappaB and p38 MAPK in mouse skin

Biofactors. 2004;21(1-4):27-31. doi: 10.1002/biof.552210107.

Abstract

[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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Anticarcinogenic Agents / pharmacology
  • Catechols
  • Cyclooxygenase 2
  • Enzyme Activation / drug effects
  • Fatty Alcohols / administration & dosage
  • Fatty Alcohols / pharmacology*
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Ginger
  • Mice
  • Mice, Inbred ICR
  • NF-kappa B / metabolism*
  • Phosphorylation
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Skin / drug effects
  • Skin / enzymology*
  • Skin / metabolism
  • Tetradecanoylphorbol Acetate / antagonists & inhibitors
  • Tetradecanoylphorbol Acetate / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Anticarcinogenic Agents
  • Catechols
  • Fatty Alcohols
  • NF-kappa B
  • gingerol
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • p38 Mitogen-Activated Protein Kinases
  • Tetradecanoylphorbol Acetate