Role of dietary polyphenols in platelet aggregation. A review of the supplementation studies (original) (raw)
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Molecular Nutrition & Food Research, 2010
Cardiovascular disease is a chronic disease influenced by many factors, with activated blood platelets being one of them. Platelets play a central role in the formation of plaques within blood vessels, contributing to early inflammatory events. Consumption of diets rich in plantbased products protects against the development of cardiovascular disease. Polyphenols, which are secondary plant metabolites found in a wide range of foodstuffs and beverages, may be partially responsible for these effects. Their protective properties include inhibitory effects on platelet function in vitro and in vivo. However, the bioavailability of many polyphenols is poor and it is unclear whether sufficient quantities can be obtained by dietary means to exert protective effects. Consequently, this review summarizes 25 well-controlled human intervention studies examining the effect of polyphenol-rich diets on platelet function. These studies report a huge variety of research methods, study designs, and study subjects, resulting in controversial assertions. One consistent finding is that cocoa-related products, however, have platelet-inhibiting effects when consumed in moderate amounts. To assess whether other classes of dietary polyphenols, or their metabolites, also beneficially affect platelet function requires more well-controlled intervention studies as well as the adoption of more uniform methods to assess platelet aggregation and activation.
Journal of Human Nutrition and Dietetics, 2013
Dietary sources of polyphenols, which are derivatives and/or isomers of flavones, isoflavones, 5 flavonols, catechins and phenolic acids possess antioxidant properties, therefore, might be important 6 in preventing oxidative-stress-induced platelet activation and attenuate adverse haemostatic function. 7 Free radicals including reactive oxygen and nitrogen species promote oxidative stress, leading to 8 platelet hyper-activation and risk of thrombosis. Consumption of antioxidant/polyphenol rich foods 9 might, therefore, impart anti-thrombotic and cardiovascular protective effects via their inhibition of 10 platelet hyper-activation or aggregation. Most commonly used antiplatelet drugs such as aspirin block 11 the cyclooxygenase-1 (COX-1) pathway of platelet activation similar to the action of antioxidants in 12 neutralizing hydrogen peroxide with a similar effect on thromboxane production via COX-1 pathway. 13 Polyphenols also target various additional platelet activation pathways e.g. by blocking platelet-ADP, 14 collagen receptors; alleviating fibrinogen binding to platelet surface (GPIIb-IIIa) receptors reducing 15 further platelet recruitment for aggregation and inhibiting platelet degranulation. Due to the ability of 16 polyphenols to target additional pathways of platelet activation, they may have the potential to 17 substitute or complement currently used anti-platelet drugs in sedentary, obese, pre-diabetic or 18 diabetic populations who can be resistant or sensitive to pharmacological antiplatelet therapy. 19 20 21 22
The role of polyphenols in cardiovascular disease
Medical science monitor : international medical journal of experimental and clinical research, 2010
Epidemiological studies suggest that diets rich in polyphenols may be associated with reduced incidence of cardiovascular disorders (mainly coronary heart disease and myocardial infarction). However, the mechanisms explaining this correlation have not been fully elucidated. Current evidence suggests that polyphenols, acting at the molecular level, improve endothelial function and inhibit platelet aggregation. In view of their antithrombotic, anti-inflammatory, and anti-aggregative properties, these compounds may play a roles in the prevention and treatment of cardiovascular disease.
Oxidative Medicine and Cellular Longevity
Cardiovascular diseases (CVD) are one of the main causes of mortality in the world. The development of these diseases has a specific factor—alteration in blood platelet activation. It has been shown that phenolic compounds have antiplatelet aggregation abilities and a positive impact in the management of CVD, exerting prominent antioxidant, anti-inflammatory, antitumor, cardioprotective, antihyperglycemic, and antimicrobial effects. Thus, this review is intended to address the antiplatelet activity of phenolic compounds with special emphasis in preventing CVD, along with the mechanisms of action through which they are able to prevent and treat CVD. In vitro and in vivo studies have shown beneficial effects of phenolic compound-rich plant extracts and isolated compounds against CVD, despite that the scientific literature available on the antiplatelet aggregation ability of phenolic compounds in vivo is scarce. Thus, despite the current advances, further studies are needed to confirm ...
Platelets, 2008
The aim of the present study was to investigate and compare the anti-platelet action of extracts from three different plants: bark of Yucca schidigera, seeds of grape and berries of Aronia melanocarpa (chokeberry). Anti-platelet action of tested extracts was compared with action of well characterized antioxidative and anti-platelet commercial monomeric polyphenol-resveratrol. The effects of extracts on platelet adhesion to collagen, collagen-induced platelet aggregation and on the production of O À 2 in resting platelets and platelets stimulated by a strong platelet agonist-thrombin were studied. The in vitro experiments have shown that all three tested extracts (5-50 mg/ml) rich in polyphenols reduce platelet adhesion, aggregation and generation of O À 2 in blood platelets. Comparative studies indicate that all three plant extracts were found to be more reactive in reduction of platelet processes than the solution of pure resveratrol. The tested extracts due to their anti-platelet effects may play an important role as components of human diet in prevention of cardiovascular or inflammatory diseases, where blood platelets are involved.
Inhibitory effect of aqueous extracts of some herbs on human platelet aggregation in vitro
Platelets, 2005
Effect of aqueous extract of several herbs on human platelet aggregation in vitro was investigated. Out of 28 herbs/ nutriceuticals investigated, camomile, nettle alfalfa, garlic and onion exhibited most significant anti-platelet activity (!45% inhibition). Aqueous extracts of alfalfa, fresh nettle, and camomile inhibited ADP induced-platelet aggregation by 73, 65 and 60%, respectively, compared with control (P < 0.05). Camomile and alfalfa inhibited collagen-induced platelet aggregation by 84 and 65%, respectively, but nettle could not inhibit collagen-induced aggregation. In contrast, nettle was the most potent inhibitor (66%) of whole blood aggregation induced by collagen, followed by alfalfa (52%), and camomile (30%) compared with control (P < 0.05). None of these three herbs however could inhibit arachidonic acid or thrombin induced platelet aggregation. Camomile and alfalfa strongly inhibited thromboxane B 2 synthesis induced by ADP or collagen, but nettle had no effect. Alfalfa and nettle increased cGMP levels in platelets by 50 and 35%, respectively, compared with the control (1.85 AE 0.23 nM) (P < 0.005). All these data indicate that camomile, nettle and alfalfa have potent anti-platelet properties, and their inhibitory actions are mediated via different mechanisms.
The effects of polyphenols in olive leaves on platelet function
Nutrition Metabolism and Cardiovascular Diseases, 2008
Introduction: The phenolic compounds of olive leaves and olive oils in the Mediterranean diet have been associated with a reduced incidence of heart disease. Accordingly, antioxidant-rich diets may prevent the deleterious effects of oxidative metabolism by scavenging free radicals, thus inhibiting oxidation and delaying atherosclerosis. The process involves phospholipase C activation and arachidonic acid metabolism, and is thought to reduce hydrogen peroxide (H 2 O 2 ). In our study, an extract of Olea europaea L. leaves was used. The active phenolic compounds in this extract are part of the secoiridoid family, known for their capacity to scavenge H 2 O 2 . The results from this study will help to improve our understanding of effects of polyphenol antioxidants in olive leaf extract on platelet function. Methods: Full blood examination (FBE), platelet aggregation, and ATP release were performed on samples from fasting, normal, healthy male subjects. Platelet function at increasing concentrations of oleuropein was investigated through measures of platelet aggregation and ATP release from activated platelets. Results: Blood analysis (n [ 11) revealed a significant dose-dependant reduction in platelet activity with olive extract concentrations of 1.0% v/v (P < 0.001). ATP Release showed a similar pattern (P [ 0.02). Conclusions: Olive leaf polyphenols derived from O. europaea L. leaves inhibited in vitro platelet activation in healthy, non-smoking males. Further bioavailability studies need to be undertaken to determine the in vivo effect of extract on platelet function and to validate the present results. ª
Cocoa and Wine Polyphenols Modulate Platelet Activation and Function
The Journal of Nutrition, 2000
There is speculation that dietary polyphenols can provide cardioprotective effects due to direct antioxidant or antithrombotic mechanisms. We report in vitro and postingestion ex vivo effects of cocoa procyanidins, a procyanidin-rich cocoa beverage and dealcoholized red wine (DRW) on human platelet activation. In a series of in vitro studies, cocoa procyanidin trimers, pentamers or DRW (3 and 10 mol/L) were incubated with citrated peripheral whole blood in the presence and absence of platelet agonists. Platelet activation was detected using fluorescent-labeled monoclonal antibodies recognizing the fibrinogen binding conformation of GPIIb-IIIa (referred to herein as PAC-1 binding) and the activation-dependent platelet epitope CD62P (P-selectin). The percentage of CD42a-positive platelets coexpressing PAC-1 binding and/or CD62P was determined by multiparameter flow cytometry. Procyanidin trimers, pentamers and DRW added to whole blood in vitro increased PAC-1 binding and P-selectin expression. In contrast, procyanidin trimers, pentamers and DRW inhibited the platelet activation in response to epinephrine. The effects on platelet activation of cocoa beverage and DRW consumption were also studied in healthy subjects. Citrated blood was obtained before and 2 and 6 h after the ingestion of a cocoa beverage, a caffeine-containing beverage, DRW or water. Platelet activation was measured by flow cytometry. The consumption of DRW did not affect the expression of activation-dependent platelet antigens, either unstimulated or after ex vivo activation with epinephrine. However, the consumption of DRW increased PAC-1 binding in response to 100 mol/L ADP ex vivo. Cocoa consumption reduced platelet response to agonists ex vivo. The ingestion of water had no effect on platelet activation, whereas a caffeine-containing beverage augmented the response of platelets to epinephrine. In summary, select cocoa procyanidins and DRW added to whole blood in vitro increased expression of platelet activation markers in unstimulated platelets but suppressed the platelet activation response to epinephrine. In contrast, cocoa consumption suppressed unstimulated and stimulated platelet activation in whole blood. This suppressive effect observed on platelet reactivity may explain in part the reported cardioprotective effects of dietary polyphenols.
Influence of flavonoids’ lipophilicity on platelet aggregation
Acta Pharmaceutica
Flavonoids are natural polyphenolic compounds present in a wide spectrum of plants that have a beneficial effect on human health. In the context of cardiovascular diseases related to plaque and thrombus formation, flavonoids exhibit an anti-aggregatory effect. Previously, it has been reported that all tested flavonoids exhibit an antiaggregatory effect on platelet aggregation when measured by impedance aggregometry on whole blood, in the test of aggregation induced by adenosine diphosphate (ADP). As not all flavonoids have the same targets within signaling pathways, an assumption of a common non-specific mechanism related to lipophilicity is to be considered. To test this hypothesis, reverse-phase thin layer chromatography was used to assess the lipophilicity of flavonoids; impedance aggregometry was used for testing of platelet aggregation and flow cytometry to monitor the influence of flavonoids on platelet activation. Lipophilicity analysis showed a highly negative correlation of...