ANTI-COAGULANT PROPERTIES OF FLAVONOID COMPOUNDS: POTENTIAL STRUCTURE-FUNCTIONAL RELATIONSHIP

Abstract

Objective: Flavonoids, naturally-occurring compounds in fruits and vegetables, possess anti-coagulant property. However, a very few studies wereattempted to understand how flavonoid structure influences its anti-coagulation property, such as clotting time. In this study, we investigatedstructurally 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-coagulantproperties 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 dosedependentmanner. 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 prolongAPTT (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. Inaddition, the prolonged APTT assay results suggested that quercetin, kaempferol, and luteolin could affect factors VIII, IX, XI, and XII of intrinsicpathway. Moreover, the synergistic effect of quercetin further enhances the heparin anti-coagulation effect. Based on our findings, we recommendthat the consumption of vegetables and fruits rich in quercetin, luteolin, and kaempferol could help prevent thrombotic stroke in high-risk patients.