scholarly journals Preparations from selected cucurbit vegetables as antiplatelet agents

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Agata Rolnik ◽  
Bartosz Skalski ◽  
Anna Stochmal ◽  
Beata Olas
Keyword(s):  
Platelet Activation ◽  
Cucurbita Pepo ◽  
Fruits And Vegetables ◽  
Thrombus Formation ◽  
Blood Platelets ◽  
Antiplatelet Agents ◽  
Blood Platelet ◽  
Arachidonic Acid Metabolism ◽  
Platelet Activity ◽  
Activated Platelets

AbstractIncreased blood platelet activation plays an important role in cardiovascular diseases (CVDs). Recent experiments indicate that certain fruits and vegetables, including onion, garlic, and beetroot, have anti-platelet potential and therefore may reduce the likelihood of CVDs. While vegetables from the Cucuritaceae family are known to exerting beneficial antioxidant and anti-inflammatory effects, their effects on blood platelet activation are poorly understood. Therefore, the aim of the present study was to determine the effect on platelet adhesion of preparations from selected cucurbits: pumpkin (Cucurbita pepo; fruit without seeds), zucchini (Cucurbita pepo convar. giromontina; fruit with seeds), cucumber (Cucumis sativus; fruit with seeds), white pattypan squash (Cucurbita pepo var. patisoniana; fruit without seeds) and yellow pattypan squash (Cucurbita pepo var. patisoniana, fruit without seeds). It also evaluates the activity of these preparations on enzymatic lipid peroxidation in thrombin-activated washed blood platelets by TBARS assay. The study also determines the anti-platelet properties of these five cucurbit preparations in whole blood by flow cytometry and with the total thrombus-formation analysis system (T-TAS) and evaluates the cytotoxicity of the tested preparations against platelets based on LDH activity. The results indicate that the yellow Cucurbita pepo var. patisoniana preparation demonstrated stronger anti-platelet properties than the other tested preparations, reducing the adhesion of thrombin-activated platelets to collagen/fibrinogen, and inhibiting arachidonic acid metabolism and GPIIb/IIIa expression on 10 µM ADP-activated platelets. None of the preparations was found to cause platelet lysis. Our findings provide new information on the anti-platelet activity of the tested cucurbit preparations and their potential for treating CVDs associated with platelet hyperactivity.

scholarly journals Preparations from Selected Cucurbit Vegetables as Antiplatelet Agents – An in Vitro Study

2021 ◽  
Author(s):  
Agata Rolnik ◽  
Bartosz Skalski ◽  
Anna Stochmal ◽  
Beata Olas
Keyword(s):  
Platelet Activation ◽  
Cucurbita Pepo ◽  
Thrombus Formation ◽  
Blood Platelets ◽  
In Vitro Study ◽  
Blood Platelet ◽  
Arachidonic Acid Metabolism ◽  
Platelet Activity ◽  
Activated Platelets

Abstract Increased blood platelet activation plays an important role in cardiovascular diseases (CVDs). Recent experiments indicate that certain fruits and vegetables, including onion, garlic, and beetroot, have anti-platelet potential and therefore may reduce the likelihood of CVDs. While vegetables from the Cucuritaceae family are known to exerting beneficial antioxidant and anti-inflammatory effects, their effects on blood platelet activation are poorly understood. Therefore, the aim of the present study was to determine the effect on platelet adhesion of preparations from selected cucurbits: pumpkin (Cucirbita pepo; fruit without seeds), zucchini (Cucurbita pepo convar. giromontina; fruit with seeds), cucumber (Cucumis sativus; fruit with seeds), white pattypan squash (Cucurbita pepo var. patisoniana; fruit without seeds) and yellow pattypan squash (Cucurbita pepo var. patisoniana, fruit without seeds). It also evaluates the activity of these preparations on enzymatic lipid peroxidation in thrombin-activated washed blood platelets by TBARS assay. The study also determines the anti-platelet and anticoagulant properties of these five cucurbit preparations in whole blood by flow cytometry and with the total thrombus-formation analysis system (T-TAS) and evaluates the cytotoxicity of the tested preparations against platelets based on LDH activity. The results indicate that the yellow Cucurbita pepo var. patisoniana preparation demonstrated stronger anti-platelet properties than the other tested preparations, reducing the adhesion of thrombin-activated platelets to collagen/fibrinogen, and inhibiting arachidonic acid metabolism and GPIIb/IIIa expression on 10 µM ADP-activated platelets. None of the preparations was found to cause platelet lysis. Our findings provide new information on the anti-platelet activity of the tested cucurbit preparations and their potential for treating CVDs associated with platelet hyperactivity.

scholarly journals Black Sorghum Phenolic Extract Modulates Platelet Activation and Platelet Microparticle Release

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1760 ◽  
Author(s):  
Borkwei Ed Nignpense ◽  
Kenneth A Chinkwo ◽  
Christopher L Blanchard ◽  
Abishek B Santhakumar
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Conformational Changes ◽  
Thrombus Formation ◽  
Antiplatelet Agents ◽  
Limited Information ◽  
Platelet Activity ◽  
Dietary Polyphenols ◽  
High Antioxidant Activity ◽  
Phenolic Extract

Platelet hyper-activation and platelet microparticles (PMPs) play a key role in the pathogenesis of cardiovascular diseases. Dietary polyphenols are believed to mimic antiplatelet agents by blunting platelet activation receptors via its antioxidant phenomenon. However, there is limited information on the anti-platelet activity of grain-derived polyphenols. The aim of the study is to evaluate the effects of sorghum extract (Shawaya short black 1 variety), an extract previously characterised for its high antioxidant activity and reduction of oxidative stress-related endothelial dysfunction, on platelet aggregation, platelet activation and PMP release. Whole blood samples collected from 18 healthy volunteers were treated with varying non-cytotoxic concentrations of polyphenol-rich black sorghum extract (BSE). Platelet aggregation study utilised 5 µg/mL collagen to target the GPVI pathway of thrombus formation whereas adenine phosphate (ADP) was used to stimulate the P2Y1/P2Y12 pathway of platelet activation assessed by flow cytometry. Procaspase-activating compound 1 (PAC-1) and P-selectin/CD62P were used to evaluate platelet activation- related conformational changes and degranulation respectively. PMPs were isolated from unstimulated platelets and quantified by size distribution and binding to CD42b. BSE treatment significantly reduced both collagen-induced platelet aggregation and circulatory PMP release at 40 µg/mL (p < 0.001) when compared to control. However, there was no significant impact of BSE on ADP-induced activation-dependent conformational change and degranulation of platelets. Results of this study suggest that phenolic rich BSE may confer cardio-protection by modulating specific signalling pathways involved in platelet activation and PMP release.

scholarly journals Anti-Platelet Properties of Phenolic Extracts from the Leaves and Twigs of Elaeagnus rhamnoides (L.) A. Nelson

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3620 ◽  
Author(s):  
Bartosz Skalski ◽  
Bogdan Kontek ◽  
Agata Rolnik ◽  
Beata Olas ◽  
Anna Stochmal ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Blood Platelets ◽  
Biological Effects ◽  
Blood Platelet ◽  
Arachidonic Acid Metabolism ◽  
Sea Buckthorn ◽  
Platelet Activity ◽  
Aronia Melanocarpa ◽  
Phenolic Extracts

Sea buckthorn (Elaeagnus rhamnoides (L.) A. Nelson) is a small tree or bush. It belongs to the Elaeagnaceae family, and has been used for many years in traditional medicine in both Europe and Asia. However, there is no data on the effect of sea buckthorn leaves and twigs on the properties of blood platelets. The aim of the study was to analyze the biological activity of phenolic extracts from leaves and twigs of sea buckthorn in blood platelets in vitro. Two sets of extracts were used: (1) phenolic compounds from twigs and (2) phenolic compounds from leaves. Their biological effects on human blood platelets were studied by blood platelet adhesion, platelet aggregation, arachidonic acid metabolism and the generation of superoxide anion. Cytotoxicity was also evaluated against platelets. The action of extracts from sea buckthorn twigs and leaves was compared to activities of the phenolic extract (a commercial product from the berries of Aronia melanocarpa (Aronox®) with antioxidative and antiplatelet properties. This study is the first to demonstrate that extracts from sea buckthorn leaves and twigs are a source of bioactive compounds which may be used for the prophylaxis and treatment of cardiovascular pathologies associated with blood platelet hyperactivity. Both leaf and twig extracts were found to display anti-platelet activity in vitro. Moreover, the twig extract (rich in proanthocyanidins) displayed better anti-platelet potential than the leaf extract or aronia extract.

scholarly journals Role of Endothelial Cells in Acute and Chronic Thrombosis

2019 ◽  
Vol 39 (02) ◽  
pp. 128-139 ◽  
Author(s):  
Magdalena L. Bochenek ◽  
Katrin Schäfer
Keyword(s):  
Endothelial Cells ◽  
Platelet Activation ◽  
Thrombus Formation ◽  
Blood Clot ◽  
Vascular Occlusion ◽  
Coagulation Factors ◽  
Activated Platelets ◽  
Endothelial Cell Response ◽  
Von Willebrand

AbstractHaemostasis encompasses a set of strictly regulated actions, such as vasoconstriction, platelet activation and blood coagulation. Endothelial cells play a crucial role in all of these processes and are an integral part of the vascular response to injury resulting in thrombus formation. Healthy endothelium expresses mediators to prevent platelet activation, including prostacyclin and nitric oxide, and to inhibit coagulation, such as thrombomodulin or RNase1. Upon activation, endothelial cells expose von Willebrand factor, integrins and other receptors to interact with activated platelets, erythrocytes and coagulation factors, respectively, resulting in blood clot formation. The endothelial cell response to cytokines and growth factors released from activated platelets and immune cells abundantly present in arterial and venous thrombi also plays an important role for thrombus resolution, whereas failure to completely resolve thrombi may initiate fibrotic remodelling and chronic vascular occlusion both in the arterial and venous tree. Therefore, endothelial cells are increasingly recognized as potential target to prevent thrombotic events and to accelerate thrombus resolution. Here, we discuss recent publications from our group in the context of other studies on the role of the endothelium during acute and chronic thrombotic events.

scholarly journals Increased Pro-Thrombotic Platelet Activity Associated with Thrombin/PAR1-Dependent Pathway Disorder in Patients with Secondary Progressive Multiple Sclerosis

2020 ◽  
Vol 21 (20) ◽  
pp. 7722
Author(s):  
Angela Dziedzic ◽  
Elzbieta Miller ◽  
Michal Bijak ◽  
Lukasz Przyslo ◽  
Joanna Saluk-Bijak
Keyword(s):  
Multiple Sclerosis ◽  
Mrna Expression ◽  
Platelet Activation ◽  
Blood Platelets ◽  
Surface Expression ◽  
Epidemiological Studies ◽  
Progressive Multiple Sclerosis ◽  
Apolipoprotein A1 ◽  
Platelet Activity ◽  
Activation Markers

Epidemiological studies confirm the high risk of ischemic events in multiple sclerosis (MS) that are associated with increased pro-thrombotic activity of blood platelets. The most potent physiological platelet agonist is thrombin, which activates platelets via cleavage of specific protease-activated receptors (PARs). Our current study is aimed to determine the potential genetics and proteomic abnormalities of PAR1 in both platelets and megakaryocytes, which may have thromboembolic consequences in the course of MS. The obtained results were correlated with the expression level of platelet and megakaryocyte transcripts for APOA1 and A2M genes encoding atherosclerosis biomarkers: apolipoprotein A1 (ApoA1) and α-2-macroglobulin (α2M), respectively. Moreover, PAR1 functionality in MS platelets was assessed by flow cytometry, determining the level of platelet–platelet and platelet–leukocyte aggregates, platelet microparticles and surface expression of P-selectin. As a PAR1 agonist, the synthetic TRAP-6 peptide was used, which made it possible to achieve platelet activation in whole blood without triggering clotting. Comparative analyses showed an elevated level of platelet activation markers in the blood of MS patients compared to controls. The mRNA expression of gene coding α2M was upregulated, whilst ApoA1 was down-regulated, both in platelets and megakaryocytes from MS patients. Furthermore, we observed an increase in both mRNA expression and surface density of PAR1 in platelets and megakaryocytes in MS compared to controls. Both the level of platelet activation markers and PAR1 expression showed a high correlation with the expression of transcripts for APOA1 and A2M genes.

DETECTION OF ACTIVATED PLATELETS IN WHOLE BLOOD BY FLOW CYTOMETRY

1987 ◽  
Author(s):  
S J Shattil ◽  
J A Hoxie ◽  
M Cunningham ◽  
C S Abrahms ◽  
J O’Brien ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Monoclonal Antibodies ◽  
Platelet Activation ◽  
Whole Blood ◽  
Thrombus Formation ◽  
Membrane Surface ◽  
White Blood Cells ◽  
Color Flow ◽  
Platelet Surface ◽  
Activated Platelets

Platelets may become activated in a number of clinical disorders and participate in thrombus formation. We have developed a direct test for activated platelets in whole blood that utilizes dual-color flow cytometry and requires no washing steps. Platelets were distinguished from erythrocytes and white blood cells in the flow cytometer by labeling the platelets with biotin-AP1, an antibody specific for membrane glycoprotein lb, and analyzing the cells for phycoerythrin-streptavidin fluorescence. Membrane surface changes resulting from platelet activation were detected with three different FITC-labeled monoclonal antibodies: 1) PAC1, an antibody specific for the fibrinogen receptor on activated platelets; 2) 9F9, which binds to the D-domain of fibrinogen and detects platelet-bound fibrinogen; and 3) S12, which binds to an alpha-granule membrane protein that associates with the platelet surface during secretion. Unstimulated platelets demonstrated no PAC1, 9F9, or S12-specific fluorescence, indicating that they did not bind these antibodies. Upon stimulation with agonists, however, the platelets demonstrated a dose-dependent increase in FITC-fluorescence. The binding of 9F9 to activated platelets required fibrinogen. Low concentrations of ADP and epinephrine, which induce fibrinogen receptors but little secretion, stimulated near-maximal PAC1 or 9F9 binding but little S12 binding. On the other hand, a concentration of phorbol myristate acetate that evokes full platelet aggregation and secretion induced maximal binding of all three antibodies. When blood samples containing activated and non-activated platelets were mixed, as few as 0.8% activated platelets could be detected by this technique. There was a direct correlation between ADP-induced FITC-PAC1 binding and binding determined in a conventional 125I-PAC1 binding assay (r = 0.99; p < 0.001). These studies demonstrate that activated platelets can be reliably detected in whole blood using activation-dependent monoclonal antibodies and flow cytometry. This method may be useful to assess the degree of platelet activation and the efficacy platelet inhibitor therapy in thrombotic disorders.

scholarly journals Noncanonical Effects of Oral Thrombin and Factor Xa Inhibitors in Platelet Activation and Arterial Thrombosis

2020 ◽  
Author(s):  
Amin Polzin ◽  
Lisa Dannenberg ◽  
Manuela Thienel ◽  
Martin Orban ◽  
Georg Wolff ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Arterial Thrombosis ◽  
Thrombus Formation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Cascade ◽  
Platelet Activity ◽  
Vein Thrombosis

AbstractNonvitamin K oral anticoagulants (NOACs) or direct oral anticoagulants comprise inhibitors of factor Xa (rivaroxaban, apixaban, edoxaban) or factor IIa (dabigatran). Both classes efficiently interfere with the final or penultimate step of the coagulation cascade and showed superior net clinical benefit compared with vitamin K antagonists for prevention of thromboembolic events in patients with AF and for prevention and therapy of deep vein thrombosis and pulmonary embolism. None the less, accumulating data suggested, that there may be differences regarding the frequency of atherothrombotic cardiovascular events between NOACs. Thus, the optimal individualized NOAC for each patient remains a matter of debate. Against this background, some basic and translational analyses emphasized NOAC effects that impact on platelet activity and arterial thrombus formation beyond inhibition of plasmatic coagulation. In this review, we will provide an overview of the available clinical and translational evidence for so-called noncanonical NOAC effects on platelet activation and arterial thrombosis.

Mechanisms of platelet activation: Need for new strategies to protect against platelet-mediated atherothrombosis

2009 ◽  
Vol 102 (08) ◽  
pp. 248-257 ◽  
Author(s):  
Lisa Jennings
Keyword(s):  
Antiplatelet Therapy ◽  
Platelet Activation ◽  
Platelet Reactivity ◽  
Thrombus Formation ◽  
Antiplatelet Agents ◽  
Bleeding Risk ◽  
Adenosine Diphosphate ◽  
Adp Receptor ◽  
Activation Pathways ◽  
New Strategies

SummaryPlatelets are central mediators of haemostasis at sites of vascular injury, but they also mediate pathologic thrombosis. Activated platelets stimulate thrombus formation in response to rupture of an atherosclerotic plaque or endothelial cell erosion, promoting atherothrombotic disease. They also interact with endothelial cells and leukocytes to promote inflammation, which contributes to atherosclerosis. Multiple pathways contribute to platelet activation, and current oral antiplatelet therapy with aspirin and a P2Y12 adenosine diphosphate (ADP) receptor antagonist target the thromboxane A2 and ADP pathways, respectively. Both can diminish activation by other factors, but the extent of their effects depends upon the agonist, agonist strength, and platelet reactivity status. Although these agents have demonstrated significant clinical benefit, residual morbidity and mortality remain high. Neither agent is effective in inhibiting thrombin, the most potent platelet activator. This lack of comprehensive inhibition of platelet function allows continued thrombus formation and exposes patients to risk for recurrent thrombotic events. Moreover, bleeding risk is a substantial limitation of antiplatelet therapy, because these agents target platelet activation pathways critical for both protective haemostasis and pathologic thrombosis. Novel antiplatelet therapies that provide more complete inhibition of platelet activation without increasing bleeding risk could considerably decrease residual risk for ischemic events. Inhibition of the protease-activated receptor (PAR)-1 platelet activation pathway stimulated by thrombin is a novel, emerging approach to achieve more comprehensive inhibition of platelet activation when used in combination with current oral antiplatelet agents. PAR-1 inhibition is not expected to increase bleeding risk, as this pathway does not interfere with haemostasis.

Anthocyanins from red cabbage extract — evidence of protective effects on blood platelets

2012 ◽  
Vol 7 (4) ◽  
pp. 655-663 ◽  
Author(s):  
Joanna Saluk ◽  
Michał Bijak ◽  
Joanna Kołodziejczyk-Czepas ◽  
Małgorzata Posmyk ◽  
Krystyna Janas ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Platelet Activation ◽  
Blood Platelets ◽  
Protective Effects ◽  
Platelet Activity ◽  
Red Cabbage ◽  
Arachidonate Cascade ◽  
Wide Range ◽  
Antioxidative Effects

AbstractRed cabbage belongs to cruciferous vegetables recognized as a rich source of anthocyanins. Anthocyanins have a wide range of therapeutic advantages without adverse effects, including cardiovascular protective properties. For development of cardiovascular diseases, platelet activation is crucial; therefore compounds which inhibit platelet activation are sought after. The anti-platelet activity of anthocyanins has only been described and is still unclear. In our study, the extract of anthocyanins, obtained from fresh leaves of red cabbage, was used in vitro to examine their antioxidative effects on platelets under oxidative stress conditions which are responsible for hyperactivity of these cells. The antiplatelet and antioxidative activities were determined by platelet aggregation and specific markers of the arachidonate cascade with O2−· generation, and oxidative changes (carbonyl groups and 3-nitrotyrosine). Extracts (5–15 μM) protected platelet proteins and lipids against oxidative damage, and diminished platelet activation. Anthocyanins from red cabbage provided beneficial anti-platelet effects and might help prevent cardiovascular diseases.

scholarly journals Oxidized LDL activates blood platelets through CD36/NOX2–mediated inhibition of the cGMP/protein kinase G signaling cascade

Blood ◽  
2015 ◽  
Vol 125 (17) ◽  
pp. 2693-2703 ◽  
Author(s):  
Simbarashe Magwenzi ◽  
Casey Woodward ◽  
Katie S. Wraith ◽  
Ahmed Aburima ◽  
Zaher Raslan ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Platelet Activation ◽  
Thrombus Formation ◽  
Blood Platelets ◽  
Oxidized Ldl ◽  
Protein Kinase G ◽  
Signaling Cascade ◽  
Key Points ◽  
Cgmp Signaling

Key Points oxLDL binds platelet CD36 to stimulate tyrosine kinase– and PKC-dependent activation of NOX2 and generation of ROS. oxLDL- and hyperlipidemia-induced ROS mediate platelet desensitization to inhibitory cGMP signaling to facilitate platelet activation and thrombus formation.

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