Gingerols and related analogues inhibit arachidonic acid-induced human platelet serotonin release and aggregation

Thromb Res. 2001 Sep 1;103(5):387-97. doi: 10.1016/s0049-3848(01)00338-3.


Gingerols, the active components of ginger (the rhizome of Zingiber officinale, Roscoe), represent a potential new class of platelet activation inhibitors. In this study, we examined the ability of a series of synthetic gingerols and related phenylalkanol analogues (G1-G7) to inhibit human platelet activation, compared to aspirin, by measuring their effects on arachidonic acid (AA)-induced platelet serotonin release and aggregation in vitro. The IC(50) for inhibition of AA-induced (at EC(50)=0.75 mM) serotonin release by aspirin was 23.4+/-3.6 microM. Gingerols and related analogues (G1-G7) inhibited the AA-induced platelet release reaction in a similar dose range as aspirin, with IC(50) values between 45.3 and 82.6 microM. G1-G7 were also effective inhibitors of AA-induced human platelet aggregation. Maximum inhibitory (IC(max)) values of 10.5+/-3.9 and 10.4+/-3.2 microM for G3 and G4, respectively, were approximately 2-fold greater than aspirin (IC(max)=6.0+/-1.0 microM). The remaining gingerols and related analogues maximally inhibited AA-induced platelet aggregation at approximately 20-25 microM. The mechanism underlying inhibition of the AA-induced platelet release reaction and aggregation by G1-G7 may be via an effect on cyclooxygenase (COX) activity in platelets because representative gingerols and related analogues (G3-G6) potently inhibited COX activity in rat basophilic leukemia (RBL-2H3) cells. These results provide a basis for the design of more potent synthetic gingerol analogues, with similar potencies to aspirin, as platelet activation inhibitors with potential value in cardiovascular disease.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Animals
  • Arachidonic Acid / pharmacology*
  • Aspirin / pharmacology
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Catechols
  • Fatty Alcohols / chemical synthesis
  • Fatty Alcohols / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Middle Aged
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / chemical synthesis
  • Platelet Aggregation Inhibitors / pharmacology
  • Prostaglandin-Endoperoxide Synthases / drug effects
  • Rats
  • Serotonin / metabolism*
  • Solubility
  • Structure-Activity Relationship
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / enzymology


  • Catechols
  • Fatty Alcohols
  • Platelet Aggregation Inhibitors
  • Arachidonic Acid
  • Serotonin
  • gingerol
  • Prostaglandin-Endoperoxide Synthases
  • Aspirin