Previous studies using washed p
late
lets demonstrated that certain f
lavonoids inhibit p
late
let function through severa
l mechanisms inc
luding b
lockade of TxA
2 receptors (TPs). We aimed to ana
lyze the binding capacity of f
lavonoids to TPs in p
late
let rich p
lasma (PRP), investigated their effect in f
lowing b
lood, and eva
luated the abi
lity of apigenin to improve the efficacy of aspirin in the inhibition of p
late
let aggregation. The binding of f
lavonoids to TPs in PRP was exp
lored using binding assays and the TP antagonist [
3H]SQ29548. Effects of f
lavonoids on p
late
let adhesion were assessed using arteria
l subendothe
lium with annu
lar p
late perfusion chambers, and g
loba
l eva
luation of apigenin on high-shear-dependent p
late
let function was determined by the PFA-100. To eva
luate the abi
lity of apigenin to potentiate the effect of aspirin, arachidonic acid-induced p
late
let aggregation was measured prior to and after consumption of subaggregatory doses of aspirin in the presence or absence of apigenin. Binding assays revea
led that apigenin was an efficient competitor of [
3H]SQ29548 binding to PRP (
Ki = 155.3
![](http://pubs.acs.org/images/entities/p<font color=)
lusmn.gif"> 65.4 µM), and perfusion studies showed that apigenin, genistein, and catechin significant
ly diminished thrombus formation when compared to contro
l (26.2
![](http://pubs.acs.org/images/entities/p<font color=)
lusmn.gif"> 3.8, 33.1
![](http://pubs.acs.org/images/entities/p<font color=)
lusmn.gif"> 5.2, and 26.2
![](http://pubs.acs.org/images/entities/p<font color=)
lusmn.gif"> 5.2 vs 76.6
![](http://pubs.acs.org/images/entities/p<font color=)
lusmn.gif"> 2.6%, respective
ly;
p &
lt; 0.05). Apigenin, simi
lar
ly to the TP antagonist SQ29548, significant
ly pro
longed co
llagen epinephrine-induced PFA-100 c
losure time in comparison to the contro
l and, when added to p
late
lets that had been exposed in vivo to aspirin, potentiated its inhibitory effect on p
late
let aggregation. The inhibitory effect of some f
lavonoids in the presence of p
lasma, particu
lar
ly apigenin, might in part re
ly on TxA
2 receptor antagonism. There is a c
lear increase in the ex vivo antip
late
let effect of aspirin in the presence of apigenin, which encourages the idea of the combined use of aspirin and certain f
lavonoids in patients in which aspirin fai
ls to proper
ly suppress the TxA
2 pathway.