Apigenin Inhibits Platelet Adhesion and Thrombus Formation and Synergizes with Aspirin in the Suppression of the Arachidonic Acid Pathway

• Published in: Journal of agricultural and food chemistry 2008-05, Vol.56 (9), p.2970-2976
• Main Authors: Navarro-Núñez, L, Lozano, M. L, Palomo, M, Martínez, C, Vicente, V, Castillo, J, Benavente-García, O, Diaz-Ricart, M, Escolar, G, Rivera, J
• Format: Article
• Language: English
• Subjects: adhesion; apigenin; Apigenin - metabolism; Apigenin - pharmacology; Arachidonic Acid - metabolism; aspirin; Aspirin - pharmacology; binding capacity; Bioactive Constituents; biochemical pathways; Biological and medical sciences; blood coagulation; blood platelets; Blood Platelets - drug effects; Blood Platelets - physiology; catechin; cell adhesion; Drug Synergism; Endothelium - physiology; Flavonoid; flavonoids; Food industries; Fundamental and applied biological sciences. Psychology; genistein; human nutrition; Humans; Hydrazines - metabolism; patients; Platelet Adhesiveness - drug effects; platelet aggregation; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; Platelet-Rich Plasma - metabolism; platelets; receptors; Receptors, Thromboxane A2, Prostaglandin H2 - antagonists & inhibitors; Receptors, Thromboxane A2, Prostaglandin H2 - metabolism; synergism; Thrombosis; thromboxanes
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf0723209

Previous studies using washed platelets demonstrated that certain flavonoids inhibit platelet function through several mechanisms including blockade of TxA2 receptors (TPs). We aimed to analyze the binding capacity of flavonoids to TPs in platelet rich plasma (PRP), investigated their effect in flowing blood, and evaluated the ability of apigenin to improve the efficacy of aspirin in the inhibition of platelet aggregation. The binding of flavonoids to TPs in PRP was explored using binding assays and the TP antagonist [3H]SQ29548. Effects of flavonoids on platelet adhesion were assessed using arterial subendothelium with annular plate perfusion chambers, and global evaluation of apigenin on high-shear-dependent platelet function was determined by the PFA-100. To evaluate the ability of apigenin to potentiate the effect of aspirin, arachidonic acid-induced platelet aggregation was measured prior to and after consumption of subaggregatory doses of aspirin in the presence or absence of apigenin. Binding assays revealed that apigenin was an efficient competitor of [3H]SQ29548 binding to PRP (K i = 155.3 ± 65.4 µM), and perfusion studies showed that apigenin, genistein, and catechin significantly diminished thrombus formation when compared to control (26.2 ± 3.8, 33.1 ± 5.2, and 26.2 ± 5.2 vs 76.6 ± 2.6%, respectively; p < 0.05). Apigenin, similarly to the TP antagonist SQ29548, significantly prolonged collagen epinephrine-induced PFA-100 closure time in comparison to the control and, when added to platelets that had been exposed in vivo to aspirin, potentiated its inhibitory effect on platelet aggregation. The inhibitory effect of some flavonoids in the presence of plasma, particularly apigenin, might in part rely on TxA2 receptor antagonism. There is a clear increase in the ex vivo antiplatelet effect of aspirin in the presence of apigenin, which encourages the idea of the combined use of aspirin and certain flavonoids in patients in which aspirin fails to properly suppress the TxA2 pathway.