Effective anti-platelet and COX-1 enzyme inhibitors from pungent constituents of ginger

Thromb Res. 2003;111(4-5):259-65. doi: 10.1016/j.thromres.2003.09.009.

Abstract

Background: Based on recent studies, pungent constituents of ginger (Zingiber officinale) and related substances represent a potential new class of anti-platelet agents. The ability of 20 pungent constituents of ginger and related substances to inhibit arachidonic acid (AA) induced platelet activation in human whole blood was studied.

Methods: Anti-platelet activity of the compounds was measured in vitro by the Chrono Log whole blood platelet aggregometer. Molecular hydrophobicity (log P) was measured by reversed-phase high-performance liquid chromatography. COX-1 (ovine) inhibitory effect of [8]-paradol and analogues 1 and 5 was carried out using a COX-1 inhibitor assay kit.

Results: [8]-Gingerol, [8]-shogaol, [8]-paradol and gingerol analogues (1 and 5) exhibited anti-platelet activities with IC(50) values ranging from 3 to 7 microM, whilst under similar conditions the IC(50) value for aspirin was 20+/-11 microM. The COX-1 inhibitory activity of [8]-paradol (IC(50)=4+/-1 microM) was more potent than the gingerol analogues (1 and 5) (IC(50) approximately 20 microM).

Conclusion: The above findings show that gingerol compounds and their derivatives are more potent anti-platelet agents than aspirin under the conditions described in this study. [8]-Paradol, a natural constituent of ginger, was found to be the most potent COX-1 inhibitor and anti platelet aggregation agent. The mechanism underlying AA-induced platelet aggregation inhibition may be related to attenuation of COX-1/Tx synthase enzymatic activity. Lastly, important features of phenolic compounds for inhibition of AA-induced platelet aggregation and COX-1 activity were revealed in this study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonic Acid / pharmacology
  • Aspirin / pharmacology
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism*
  • Cells, Cultured
  • Cyclooxygenase 1
  • Dose-Response Relationship, Drug
  • Ginger / metabolism*
  • Humans
  • Isoenzymes / antagonists & inhibitors*
  • Isoenzymes / blood*
  • Isoenzymes / metabolism
  • Membrane Proteins
  • Phenols / pharmacology*
  • Plant Extracts / pharmacology*
  • Platelet Activation / drug effects
  • Platelet Aggregation / drug effects*
  • Prostaglandin-Endoperoxide Synthases / blood*
  • Prostaglandin-Endoperoxide Synthases / metabolism

Substances

  • Isoenzymes
  • Membrane Proteins
  • Phenols
  • Plant Extracts
  • Arachidonic Acid
  • Cyclooxygenase 1
  • PTGS1 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Aspirin