Natural Polyphenols May Normalize Hypochlorous Acid-Evoked Hemostatic Abnormalities in Human Blood

Area of Science:

• Biochemistry
• Hematology
• Pharmacology

Background:

• Neutrophils secrete myeloperoxidase (MPO) during pathogen invasion, producing hypochlorous acid (HOCl).
• High HOCl concentrations can disrupt hemostasis, inhibiting platelet aggregation and thrombus formation, while increasing fibrin density and reducing fibrinolysis.
• Plant-derived polyphenols possess antioxidant properties that may modulate HOCl-induced hemostatic dysfunction.

Purpose of the Study:

• To investigate the effects of quercetin (Que), epigallocatechin gallate (EGCG), and resveratrol (Resv) on HOCl-induced hemostatic abnormalities.
• To determine if these polyphenols, at non-platelet-affecting concentrations, can normalize disturbed hemostasis.
• To differentiate the specific impacts of Que, EGCG, and Resv on platelet aggregation, thrombus formation, fibrin density, and fibrinolysis.

Main Methods:

• Platelet-rich plasma was used to assess HOCl-evoked inhibition of platelet aggregation via optical methods.
• Thrombus formation under flow conditions was evaluated in whole blood using confocal microscopy.
• Fibrin density was quantified using confocal microscopy, and fibrinolysis was measured turbidimetrically in plasma samples.

Main Results:

• Que (5-25 μM) and EGCG (10-25 μM) abolished HOCl-induced inhibition of platelet aggregation.
• Resveratrol (10-25 μM) enhanced HOCl's inhibitory effect on platelet aggregation and thrombus formation.
• Que, EGCG, and Resv (5-25 μM) normalized HOCl-induced increases in fibrin density and prolonged fibrinolysis.

Conclusions:

• Que and EGCG show potential for normalizing hemostatic abnormalities during inflammation with elevated HOCl.
• Resveratrol was found to potentiate the inhibitory effects of HOCl on platelet function.
• These findings highlight the differential effects of polyphenols on HOCl-mediated hemostatic changes.