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

  • PHISIT POUYFUNG Division of Occupational Health and Safety, School of Public Health, Walailak University, Nakhon Si Thammarat 80161, Thailand
  • SURIYAN SUKATI Department of Medical Technology, School of Allied Health Sciences, Walailak University Nakhon Si Thammarat 80161, Thailand

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 dosedependent
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.

Keywords: Flavonoids, Quercetin, Activated partial thromboplastin time assay, PT assay, Anti-coagulant

References

1. World Health Organization. The Top 10 Causes of Death: Leading
Causes of Death by Economy Income Group. 2016. Available from:
https://www.who.int/news-room/fact-sheets/detail/the-top-10-causesof-
death. [Last accessed on 2019 Oct 30].
2. Alloubani A, Saleh A, Abdelhafiz I. Hypertension and diabetes
mellitus as a predictive risk factors for stroke. Diabetes Metab Syndr
2018;12:577-84.
3. Braunwald E. Diabetes, heart failure, and renal dysfunction: The
vicious circles. Prog Cardiovasc Dis 2019;62:298-302.
4. Dokken BB. The pathophysiology of cardiovascular disease
and diabetes: Beyond blood pressure and lipids. Diabetes Spectr
2008;21:160-5.
5. Alquwaizani M, Buckley L, Adams C, Fanikos J. Anticoagulants: A
review of the pharmacology, dosing, and complications. Curr Emerg
Hosp Med Rep 2013;1:83-97.
6. De Caterina R, Husted S, Wallentin L, Andreotti F, Arnesen H,
Bachmann F, et al. General mechanisms of coagulation and targets
of anticoagulants (Section I). Position paper of the esc working group
on thrombosis--task force on anticoagulants in heart disease. Thromb
Haemost 2013;109:569-79.
7. Harter K, Levine M, Henderson SO. Anticoagulation drug therapy: A
review. West J Emerg Med 2015;16:11-7.
8. Labuz-Roszak B, Machowska-Majchrzak A, Skrzypek M,
Mossakowska M, Chudek J, Wiecek A, et al. Antiplatelet and
anticoagulant therapy in elderly people with Type 2 diabetes
mellitus in Poland (based on the PolSenior Study). Arch Med Sci
2017;13:1018-24.
9. Shoeb M, Fang MC. Assessing bleeding risk in patients taking
anticoagulants. J Thromb Thrombolysis 2013;35:312-9.
10. Xiao J. Dietary flavonoid aglycones and their glycosides: Which show
better biological significance? Crit Rev Food Sci Nutr 2017;57:1874-905.
11. Welsby IJ, JonesWL, Arepally G, De Lange F, Yoshitani K, Phillips-
Bute B, et al. Effect of combined anticoagulation using heparin
and bivalirudin on the hemostatic and inflammatory responses to
cardiopulmonary bypass in the rat. Anesthesiology 2007;106:295-301.
12. Mao W, Li H, Li Y, Zhang H, Qi X, Sun H, et al. Chemical characteristic
and anticoagulant activity of the sulfated polysaccharide isolated
from Monostroma latissimum (Chlorophyta). Int J Biol Macromol
2009;44:70-4.
13. Piazza G, Goldhaber SZ, Kroll A, Goldberg RJ, Emery C, Spencer FA.
Venous thromboembolism in patients with diabetes mellitus. Am J Med
2012;125:709-16.
14. Akram M, Rashid A. Anti-coagulant activity of plants: Mini review. J
Thromb Thrombolys 2017;44:1-6.
15. Gray E, Hogwood J, Mulloy B. The anticoagulant and antithrombotic
mechanisms of heparin. Handb Exp Pharmacol 2012;207:43-61.
16. Kuntic V, Filipovic I, Vujic Z. Effects of rutin and hesperidin and their
Al(III) and Cu(II) complexes on in vitro plasma coagulation assays.
Molecules 2011;16:1378-88.
17. Manolove L, Moessmer CM, Nicolova I, Danchev N. Synthesis
and anticoagulant activities of substituted 2,4-diketochromans,
biscoumarins, and chromanocoumarins. Arch Pharm Chem. Life Sci
2006;339:319-26.
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POUYFUNG, P., & SUKATI, S. (2021). ANTI-COAGULANT PROPERTIES OF FLAVONOID COMPOUNDS: POTENTIAL STRUCTURE-FUNCTIONAL RELATIONSHIP. International Journal of Applied Pharmaceutics, 13(1), 9-12. https://doi.org/10.22159/ijap.2021.v13s1.Y0050
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