Tailoring naringenin conjugates with amplified and triple antiplatelet activity profile: Rational design, synthesis, human plasma stability and in vitro evaluation

Stylos, Evgenios Κ.; Chatziathanasiadou, Μaria V.; Tsiailanis, Antonis D.; Kellici, Tahsin F.; Tsoumani, Maria; Kostagianni, Androniki D.; Deligianni, Maria; Tselepis, Alexandros D.; Tzakos, Andreas G.

doi:10.1016/j.bbagen.2017.08.018

Cited by 15 publications

(4 citation statements)

References 53 publications

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“…The antiplatelet activity of the fatty acids and antiplatelet drugs was studied in platelet-rich plasma (PRP) by the Light transmittance aggregometry (LTA) assay, as we previously described [27][28][29] . Briefly, PRP was prepared from citrated blood samples withdrawn from peripheral venous blood of apparently healthy volunteers and the platelet number was adjusted to 250 × 10 6 /mL with homologous plateletpoor plasma (PPP).…”

Section: Platelet Aggregation Studiesmentioning

confidence: 99%

The synergistic effect of EPA and DHA with cyclooxygenase-1 inhibitors on platelet aggregation

Argyropoulou,

Tsouka,

Pantazi

et al. 2023

JAPT

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Aim: Consumption of omega-3 fatty acids docosahexaenoic acid (DHA, 22:6ω-3) and eicosapentaenoic acid (EPA, 20:5ω-3) from a variety of foods and supplements could reduce cardiovascular events. The antiplatelet drugs aspirin (ASA) and triflusal, bind to platelet cyclooxygenase-1, thus preventing the biosynthesis of thromboxane A2 from arachidonic acid. ASA, triflusal, and their combinations with DHA or EPA were evaluated against in vitro platelet aggregation induced by the agonists AA, ADP, or TRAP-6. Materials-Methods: Platelet Rich Plasma (PRP), isolated from blood of healthy volunteers was pre-incubated with acetylsalicylic acid, triflusal, EPA, DHA, or the drug-omega-3 combinations at various concentrations for 10min at 37ºC, prior to activation by AA, TRAP-6, and ADP (0.3mM, 10μM and 6μM, respectively). Platelet aggregation was determined by Light Transmittance Aggregometry. Results: DHA significantly improves ASA and triflusal’s inhibitory effect towards AA-induced platelet aggregation, while EPA enhanced only the antiplatelet activity of ASA. Moreover, only the combination of ASA with EPA exhibited enhanced inhibitory effect against platelet aggregation induced by ADP. Furthermore, the inhibition of ASA and triflusal on TRAP-6-induced platelet aggregation was enhanced when ASA or triflusal were combined with EPA. Conclusions: Both DHA and EPA inhibit AA, ADP and TRAP-6-induced platelet aggregation in a dose dependent manner. The results of this study suggest a potentially beneficial use of EPA and DHA supplementation, in conjunction with the antiplatelet drugs ASA and triflusal.

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Section: Platelet Aggregation Studiesmentioning

confidence: 99%

The synergistic effect of EPA and DHA with cyclooxygenase-1 inhibitors on platelet aggregation

Argyropoulou,

Tsouka,

Pantazi

et al. 2023

JAPT

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“…Platelet-rich plasma was prepared under sterile conditions by centrifugation of citrated whole blood at 126 � g for 15 minutes at room temperature, as previously described. 24,25 Platelet-poor plasma (PPP) was prepared under sterile conditions by centrifugation of autologous blood at 1500 � g for 15 minutes at room temperature, as previously described. 24,25 The present study was performed in accordance with the Declaration of Helsinki.…”

Section: Preparation Of Platelet-rich Plasmamentioning

confidence: 99%

“…24,25 Platelet-poor plasma (PPP) was prepared under sterile conditions by centrifugation of autologous blood at 1500 � g for 15 minutes at room temperature, as previously described. 24,25 The present study was performed in accordance with the Declaration of Helsinki. All healthy volunteers had given informed consent and the study was approved by the Ethics Committee of the University Hospital of Ioannina.…”

Section: Preparation Of Platelet-rich Plasmamentioning

confidence: 99%

The Effect of Platelet-Rich Plasma on Endothelial Progenitor Cell Functionality

et al. 2021

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Platelets mediate circulating endothelial progenitor cell (EPC) recruitment and maturation, participating in vascular repair, however the underlying mechanism(s) remain unclear. We investigated the effect of platelet-rich plasma (PRP) on the functionality of CD34+-derived late-outgrowth endothelial cells (OECs) in culture. Confluent OECs were coincubated with PRP under platelet aggregation (with adenosine diphosphate; ADP) and nonaggregation conditions, in the presence/absence of the reversible P2Y12 platelet receptor antagonist ticagrelor. Outgrowth endothelial cell activation was evaluated by determining prostacyclin (PGI2) and monocyte chemoattractant protein-1 (MCP-1) release and intercellular adhesion molecule-1 (ICAM-1) membrane expression. Similar experiments were performed using human umbilical vein endothelial cells (HUVECs). Platelet-rich plasma increased ICAM-1 expression and PGI2 and MCP-1 secretion compared with autologous platelet-poor plasma, whereas ADP-aggregated platelets in PRP did not exhibit any effect. Platelet-rich plasma pretreated with ticagrelor prior to activation with ADP increased all markers to a similar extent as PRP. Similar results were obtained using HUVECs. In conclusion, PRP induces OEC activation, a phenomenon not observed when platelets are aggregated with ADP. Platelet inhibition with ticagrelor restores the PRP capability to activate OECs. Since EPC activation is important for endothelial regeneration and angiogenesis, we suggest that agents inhibiting platelet aggregation, such as ticagrelor, may promote platelet-EPC interaction and EPC function.

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“…Other potential antioxidant therapeutic approaches in humans are N-acetylcysteine, an antioxidant precursor of the synthesis of GSH, or nutritional supplements mainly included in the Mediterranean diet such as polyphenols present in extra virgin olive oil, chocolate, red wine or black and green tea, which in general seems to be associated with lower CVD (reviewed in detail by Violi et al [ 8 ]). In this line of evidence, novel antiplatelet and antithrombotic therapies using different antioxidant compounds including flavonoid conjugates, isoquercetine or N-acetylcysteine are being tested [ 135 , 136 , 137 ]; however, the influence of their antioxidant activity to the antithrombotic and antiplatelet activities remains to be established.…”

Section: Antioxidants As a Potential Therapeutic Strategy To Prevementioning

confidence: 99%

Oxidative Stress in Human Atherothrombosis: Sources, Markers and Therapeutic Targets

Martin-Ventura

Rodrigues‐Díez

Martínez-López

et al. 2017

IJMS

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Atherothrombosis remains one of the main causes of morbidity and mortality worldwide. The underlying pathology is a chronic pathological vascular remodeling of the arterial wall involving several pathways, including oxidative stress. Cellular and animal studies have provided compelling evidence of the direct role of oxidative stress in atherothrombosis, but such a relationship is not clearly established in humans and, to date, clinical trials on the possible beneficial effects of antioxidant therapy have provided equivocal results. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is one of the main sources of reactive oxygen species (ROS) in human atherothrombosis. Moreover, leukocyte-derived myeloperoxidase (MPO) and red blood cell-derived iron could be involved in the oxidative modification of lipids/lipoproteins (LDL/HDL) in the arterial wall. Interestingly, oxidized lipoproteins, and antioxidants, have been analyzed as potential markers of oxidative stress in the plasma of patients with atherothrombosis. In this review, we will revise sources of ROS, focusing on NADPH oxidase, but also on MPO and iron. We will also discuss the impact of these oxidative systems on LDL and HDL, as well as the value of these modified lipoproteins as circulating markers of oxidative stress in atherothrombosis. We will finish by reviewing some antioxidant systems and compounds as therapeutic strategies to prevent pathological vascular remodeling.

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Tailoring naringenin conjugates with amplified and triple antiplatelet activity profile: Rational design, synthesis, human plasma stability and in vitro evaluation

Cited by 15 publications

References 53 publications

The synergistic effect of EPA and DHA with cyclooxygenase-1 inhibitors on platelet aggregation

The synergistic effect of EPA and DHA with cyclooxygenase-1 inhibitors on platelet aggregation

The Effect of Platelet-Rich Plasma on Endothelial Progenitor Cell Functionality

Oxidative Stress in Human Atherothrombosis: Sources, Markers and Therapeutic Targets

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