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 IC50 values ranging from 3 to 7 μM, whilst under similar conditions the IC50 value for aspirin was 20±11 μM. The COX-1 inhibitory activity of [8]-paradol (IC50=4±1 μM) was more potent than the gingerol analogues (1 and 5) (IC50 approximately 20 μM). 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.
Keywords
Abbreviations:
AA (arachidonic acid), ASA (aspirin), COX-1/Tx (cyclooxygenase-1/thromboxane), TxA2 (thromboxane A2), SAR (structure–activity relationship), log P (logarithm of octanol–water partition coefficient), G (gingerols), S (shogaols), P (paradols), Gd (gingerdiols)To read this article in full you will need to make a payment
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Article info
Publication history
Accepted:
September 16,
2003
Received in revised form:
August 18,
2003
Received:
April 15,
2003
Identification
Copyright
© 2003 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
