A polyphenol-rich diet has beneficial effects on cardiovascular health. However, dietary polyphenols generally have low bioavailability and reach low plasma concentrations. Small phenolic metabolites of these compounds formed by human microbiota are much more easily absorbable and could be responsible for this effect. One of these metabolites, 4-methylcatechol (4-MC), was suggested to be a potent anti-platelet compound. The effect of 4-MC was tested ex vivo in a group of 53 generally healthy donors using impedance blood aggregometry. The mechanism of action of this compound was also investigated by employing various aggregation inducers/inhibitors and a combination of aggregometry and enzyme linked immunosorbent assay (ELISA) methods. 4-MC was confirmed to be more potent than acetylsalicylic acid on both arachidonic acid and collagen-triggered platelet aggregation. Its clinically relevant effect was found even at a concentration of 10 μM. Mechanistic studies showed that 4-MC is able to block platelet aggregation caused by the stimulation of different pathways (receptors for the von Willebrand factor and platelet-activating factor, glycoprotein IIb/IIIa, protein kinase C, intracellular calcium elevation). The major mechanism was defined as interference with cyclooxygenase-thromboxane synthase coupling. This study confirmed the strong antiplatelet potential of 4-MC in a group of healthy donors and defined its mechanism of action.

The 3rd Department of Internal Medicine Metabolic Care and Gerontology University Hospital and Faculty of Medicine in Hradec Králové Charles University 50005 Hradec Kralove Czech Republic

The Department of Analytical Chemistry Faculty of Pharmacy in Hradec Králové Charles University 50005 Hradec Kralove Czech Republic

The Department of Clinical Biochemistry and Diagnostics University Hospital Hradec Králové 50005 Hradec Kralove Czech Republic

The Department of Military Internal Medicine and Military Hygiene Faculty of Military Health Sciences University of Defence 50001 Hradec Kralove Czech Republic

The Department of Occupational Medicine University Hospital and Faculty of Medicine in Hradec Králové Charles University 50005 Hradec Kralove Czech Republic

The Department of Pharmacognosy and Pharmaceutical Botany Faculty of Pharmacy in Hradec Králové Charles University 50005 Hradec Kralove Czech Republic

The Department of Pharmacology and Toxicology Faculty of Pharmacy in Hradec Králové Charles University 50005 Hradec Kralove Czech Republic

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Rapid method for screening of both calcium and magnesium chelation with comparison of 21 known metal chelators

The Impact of Convertase Subtilisin/Kexin Type 9 Monoclonal Antibodies with and without Apheresis on Platelet Aggregation in Familial Hypercholesterolemia

The Effect of 4-Methylcatechol on Platelets in Familial Hypercholesterolemic Patients Treated with Lipid Apheresis and/or Proprotein Convertase Subtilisin Kexin 9 Monoclonal Antibodies