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


CONCLUSIONS
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.
Nurtjahja-Tjendraputra
Effie
E
Herbal Medicines Research and Education Center, Faculty of Pharmacy, University of Sydney, NSW 2006, Australia.
Ammit
Alaina J
AJ
Roufogalis
Basil D
BD
Tran
Van H
VH
Duke
Colin C
CC
D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D004305:Dose-Response Relationship, Drug; D020939:Zingiber officinale / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000097:blood* / Q000378:metabolism; D008565:Membrane Proteins; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood* / Q000378:metabolism
D007527:Isoenzymes; D008565:Membrane Proteins; D010636:Phenols; D010936:Plant Extracts; D016718:Arachidonic Acid; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin