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Influence of flavonoids’ lipophilicity on platelet aggregation

Flavonoids are natural polyphenolic compounds present in wide spectrum of plants that have beneficial effect on human health. In context of cardiovascular diseases related to plaque and thrombus formation, flavonoids exhibit antiaggregatory effect. Previously, it has been reported that all tested flavonoids exhibit antiaggregatory effect on platelet aggregation when measured by impedance aggregometry on whole blood, in test of aggregation induced by adenosine diphosphate (ADP). As not all flavonoids have same targets within signaling pathways, an assumption of common non-specific mechanism related to lipophilicity is to be considered. To test this hypothesis, reverse-phase thin layer chromatography was used to assess the lipophilicity of flavonoids ; impedance aggregometry was used for testing of platelet aggregation and flow cytometry to monitor the influence of flavonoids on platelet activation. Lipophilicity analysis showed highly negative correlation of logP and MINaAC for groups of flavones and flavanones. As determined by flow cytometry, the exposition of receptors necessary for promotion of platelet activation and primary clot formation was diminished, i.e., lowered expression of activated form of integrin αIIbβ3 was observed in the presence of flavanones. Platelet membrane stabilization by flavonoids as mechanism of anitaggregatory effect has been supported by impedance aggregometry experiments when specific inhibitors of platelet aggregation signaling pathways (U73122, indomethacin, verapamil) were used in the presence of a weak (ADP) and a strong (TRAP-6) agonist of aggregation. While individual flavonoids can have specific targets within aggregation signaling pathways, all flavonoids share a common non-specific mechanism of platelet aggregation inhibition related to their lipophilicity and membrane stabilization that, to some extend contributes to their antiaggregatory effect.

flavonoids, platelets ; lipophilicity ; flow cytometry ; antiaggregatory activity

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