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. 2022 Feb 8;27(3):1146.
doi: 10.3390/molecules27031146.

Flavonoids: Antiplatelet Effect as Inhibitors of COX-1

Cristina Zaragozá  1 , Miguel Ángel Álvarez-Mon  2   3   4 , Francisco Zaragozá  1 , Lucinda Villaescusa  1
Affiliations

Flavonoids: Antiplatelet Effect as Inhibitors of COX-1

Cristina Zaragozá et al. Molecules. .

Abstract

Flavonoids are compounds with a benzopyranic structure that exhibits multiple pharmacological activities. They are known for their venotonic activity, but their mechanism of action remains unclear. It is thought that, as this mechanism is mediated by prostaglandins, these compounds may interfere with the arachidonic acid (AA) cascade. These assays are designed to measure the antiplatelet aggregation capacity of quercetin, rutin, diosmetin, diosmin, and hidrosmin, as well as to evaluate a potential structure-activity ratio. In this paper, several studies on platelet aggregation at different concentrations (from 0.33 mM to 1.5 mM) of different flavone compounds are conducted, measuring platelet aggregation by impedance aggregometry, and the cyclooxygenase (COX) activity by metabolites generated, including the activity of the pure recombinant enzyme in the presence of these polyphenols. The results obtained showed that quercetin and diosmetin aglycones have a greater antiplatelet effect and inhibit the COX enzyme activity to a greater extent than their heterosides; however, the fact that greater inhibition of the pure recombinant enzyme was achieved by heterosides suggests that these compounds may have difficulty in crossing biological membranes. In any case, in view of the results obtained, it can be concluded that flavonoids could be useful as coadjuvants in the treatment of cardiovascular pathologies.

Keywords: antiplatelet activity; arachidonic acid (AA); cyclooxygenase (COX); flavonoids; impedance aggregometry; malondialdehyde (MDA); thromboxane B2 (TXB2).

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Conflict of interest statement

The authors declare there is no conflict of interest whatsoever. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Flavonoids tested: (A) quercetin; (B) rutin; (C) diosmetin; (D) diosmin; (E) hidrosmin.
Figure 2
Figure 2
Platelet aggregation generated in the presence of each flavonoid in WB samples with ADP and AA ((A) and (B) panels, respectively), and in PRP samples with ADP and AA ((C) and (D) panels, respectively). Error bars indicate the standard deviation. Color bars describe the mean and standard deviation for N = 8. * p < 0.05: statistically significant variations in platelet aggregation between samples with and without the assayed flavonoid.
Figure 3
Figure 3
MDA production is represented as the COX-1 activity in the presence of indomethacin (panel (A)) and each flavonoid at different concentrations (panel (B)). Error bars indicate the standard deviation. Color bars describe the mean and standard deviation for N = 8. * p < 0.05: significant variations respecting COX-1 activity in presence or absence of the assayed compounds.
Figure 4
Figure 4
This diagram shows h-COX-1 works in presence of indomethacin as a positive control (panel (A)) and with different concentrations of each flavonoid (panel (B)). Error bars indicate the standard deviation. Color bars describe the mean and standard deviation for N = 8. * p < 0.05: significant variations of h-COX-1 in the presence or absence of the assayed compounds.
Figure 5
Figure 5
TXB2 production is represented as COX-1 activity in the presence of indomethacin (A) and each flavonoid at different concentrations (B). Error bars indicate the standard deviation. Color bars describe the mean and standard deviation for N = 8. * p < 0.05: significant variations respecting the COX-1 activity in the presence or absence of the assayed compounds.
Figure 6
Figure 6
Calibration absorbance curves of MDA in PSS and PRP. (A) Range from 0.1 to 1 µM and linear fitting in PRP samples (r = 0.997). (B) Range from 1 to 10 µM and linear fitting in PRP samples (r = 0.994).
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