Interference of selected flavonoid aglycons in platelet aggregation assays

Mirza Bojić 1 , Željko Debeljak, Marica- Medić-Šarić 1 ,  and Maja Tomičić 3
  • 1 Faculty of Pharmacy and Biochemistry, Department of Medicinal Chemistry, University of Zagreb, Zagreb, Croatia
  • 2 Department of Clinical Laboratory Diagnostics, Clinical Hospital Center Osijek, Osijek, Croatia
  • 3 Croatian Institute of Transfusion Medicine, Department of Platelet and Leukocyte Immunology, Zagreb, Croatia


Background: Flavonoids are widely distributed across the plant kingdom and are therefore common ingredients in an everyday diet. Some flavonoids have a potential to affect platelet aggregation; most often antiaggregatory effects of flavonoids are observed. The objective of this research was to evaluate the in vitro effect of a selected set of flavonoids on platelet aggregation in whole blood.

Methods: The effect of five selected flavonoids (pinocembrin-7-methylether, epicatechin, hesperetin, 6-hydroxyflavone and 3,6-dihydroxyflavone) on platelet aggregation was studied in the citrated whole blood samples collected from 75 healthy volunteers. A Multiplate® impedance analyzer and five different aggregation inducers (ADP, arachidonic acid, collagen, ristocetin and TRAP-6) were utilized for the analysis of samples.

Results: Minimal antiaggregatory concentrations (MINaAC) of flavonoids in individual tests were reported in the following ranges: 0.12–1.91 μM; 15.26–244.14 μM; 15.26–122.07 μM; and 0.06–15.26 μM for ADP, collagen, TRAP-6 and ristocetin aggregation-inducers, respectively. When arachidonic acid was used for induction of platelet aggregation, a proaggregatory effect was observed for pinocembrin-7-methylether, epicatechin, hesperetin and 3,6-dihydroxyflavone, while the expected antiaggregatory effect was observed only for 6-hydroxyflavone (MINaAC=7.63 μM).

Conclusions: Flavonoids interfere with in vitro platelet aggregation assays exhibiting either anti- or proaggregatory effects in concentration ranges that can be achieved in circulation by dietary intake. Thus, dietary intake of flavonoids should be taken into account when interpreting the results of whole blood platelet aggregation.

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Clinical Chemistry and Laboratory Medicine ( CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. CCLM welcomes contributions on the progress in fundamental and applied research and cutting-edge clinical laboratory medicine. It is one of the leading journals in the field, with an impact factor of over three. CCLM is the official journal of nine national clinical societies and associated with EFLM.