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

      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)
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