Abstract

Objective: Flavonoids, naturally-occurring compounds in fruits and vegetables, possess anti-coagulant property. However, a very few studies were attempted to understand how flavonoid structure influences its anti-coagulation property, such as clotting time. In this study, we investigated structurally similar flavonoid compounds which differ in the number of hydroxyl groups and compared their anti-coagulation properties. Methods: We selected and evaluated five flavonoid compounds, that is, chrysin, apigenin, luteolin, kaempferol, and quercetin, for their anti-coagulant properties using in vitro prothrombin time (PT) assays and activated partial thromboplastin time (APTT) assay. Results: Our findings suggested that quercetin, kaempferol, and luteolin showed a significant anti-coagulant effect on APTT (p<0.05) in a dose-dependent manner. The dose of 500 µM quercetin showed potent prolong APTT with 37.43±1.60 s, followed by 500 µM of kaempferol and luteolin (34.63±1.29 s and 4.83±1.56 s, respectively). Furthermore, a combination of 500 µM of quercetin with 0.25 U/ml of heparin demonstrated prolong APTT (52.16±5.18 s) when compared with individual effects of either 0.25 U/ml heparin (33.4±0.50 s) or 500 µM quercetin (37.43±1.62 s) alone. Conclusion: Our results demonstrated that numbers of the hydroxyl group on flavonoid compounds influence anti-coagulation properties. In addition, the prolonged APTT assay results suggested that quercetin, kaempferol, and luteolin could affect factors VIII, IX, XI, and XII of intrinsic pathway. Moreover, the synergistic effect of quercetin further enhances the heparin anti-coagulation effect. Based on our findings, we recommend that the consumption of vegetables and fruits rich in quercetin, luteolin, and kaempferol could help prevent thrombotic stroke in high-risk patients.