Antiplatelet Potential Research Articles

Antiplatelet Activity of Phenolic Compounds-Fortified Merlot Wine and Pure Phenolic Compounds

Red wines and their pomace are valuable sources of phenolic compounds (PCs), which have been proposed as potential contributors to their cardioprotective effect through the inhibition of platelet aggregation. The antiplatelet activity of an extract depends on its chemical composition, specifically the presence of certain phenolic compounds, as well as the interactions between them affecting biological activity. In order to assess the effect on platelet aggregation, we investigated the effect of the grape pomace PC enrichment of a Merlot wine, as well as the effect of the five major phenolic compounds present in wine extracts: caffeic acid, gallic acid, quercetin, epicatechin, and catechin. We analyzed how their combination influenced platelet aggregation. We found that the fortified wine sample with the highest PC content (W8) exhibited a potent antiplatelet effect in aggregation and platelet activation assays induced by the agonists TRAP-6, collagen, and ADP, with its activity being most potent against the latter agonist (78 ± 4%). Among the evaluated phenolic compounds, quercetin showed the highest antiplatelet potential against all three agonists studied, while gallic acid showed minimal antiplatelet effect. These findings suggest that the cardioprotective effect of wines is related to their chemical composition and the synergy among phenolic compounds. However, further research is required to fully understand the underlying mechanisms and clinical relevance of this activity.

New Findings Regarding the Effects of Selected Blue Food Colorants (Genipin, Patent Blue V, and Brilliant Blue FCF) on the Hemostatic Properties of Blood Components In Vitro.

Natural and synthetic colorants present in food can modulate hemostasis, which includes the coagulation process and blood platelet activation. Some colorants have cardioprotective activity as well. However, the effect of genipin (a natural blue colorant) and synthetic blue colorants (including patent blue V and brilliant blue FCF) on hemostasis is not clear. In this study, we aimed to investigate the effects of three blue colorants-genipin, patent blue V, and brilliant blue FCF-on selected parameters of hemostasis in vitro. The anti- or pro-coagulant potential was assessed in human plasma by measuring the following coagulation times: thrombin time (TT), prothrombin time (PT), and activated partial thromboplastin time (APTT). Moreover, we used the Total Thrombus formation Analysis System (T-TAS, PL-chip) to evaluate the anti-platelet potential of the colorants in whole blood. We also measured their effect on the adhesion of washed blood platelets to fibrinogen and collagen. Lastly, the cytotoxicity of the colorants against blood platelets was assessed based on the activity of extracellular lactate dehydrogenase (LDH). We observed that genipin (at all concentrations (1-200 µM)) did not have a significant effect on the coagulation times (PT, APTT, and TT). However, genipin at the highest concentration (200 µM) and patent blue V at the concentrations of 1 and 10 µM significantly prolonged the time of occlusion measured using the T-TAS, which demonstrated their anti-platelet activity. We also observed that genipin decreased the adhesion of platelets to fibrinogen and collagen. Only patent blue V and brilliant blue FCF significantly shortened the APTT (at the concentration of 10 µM) and TT (at concentrations of 1 and 10 µM), demonstrating pro-coagulant activity. These synthetic blue colorants also modulated the process of human blood platelet adhesion, stimulating the adhesion to fibrinogen and inhibiting the adhesion to collagen. The results demonstrate that genipin is not toxic. In addition, because of its ability to reduce blood platelet activation, genipin holds promise as a novel and valuable agent that improves the health of the cardiovascular system and reduces the risk of cardiovascular diseases. However, the mechanism of its anti-platelet activity remains unclear and requires further studies. Its in vivo activity and interaction with various anti-coagulant and anti-thrombotic drugs, including aspirin and its derivatives, should be examined as well.

Overcoming the challenge of potent endogenous interferences in limaprost quantification: An innovative methodology combining differential mobility spectrometry with LC-MS/MS for ultra-high sensitivity, selectivity and significantly enhanced throughput

Limaprost, an orally administered analogue of prostaglandin E1, possesses potent vasodilatory, antiplatelet, and cytoprotective properties. Due to its extremely low therapeutic doses and exceedingly low plasma concentrations, the pharmacokinetic and bioequivalence studies of limaprost necessitate a highly sensitive quantitative method with a sub-pg/mL level of lower limit of quantification. Moreover, the intensity of endogenous interferences can even exceed the maximum concentration level of limaprost in human plasma, presenting further challenge to the quantification of limaprost. As a result, existing methods have not yet met the necessary level of sensitivity, selectivity, and throughput needed for the quantitative analysis of limaprost in pharmacokinetic and bioequivalence investigations. This study presents a new methodology that combines differential mobility spectrometry (DMS) with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and utilizes a distinctive strategy to achieve more accurate DMS conditions. This integration yields a method that is currently the most sensitive and features the shortest analytical time, making it the sole technique capable of meeting the requirements for limaprost pharmacokinetic and bioequivalence investigations. This method demonstrates robustness and is successfully employed in a pharmacokinetic investigation of limaprost in human subjects, underscoring that the combination of DMS with LC-MS/MS serves as an efficacious strategy for overcoming the challenges inherent in analyzing biological samples afflicted by multiple interferences.

The Multifaceted Effects of Non-Steroidal and Non-Opioid Anti-Inflammatory and Analgesic Drugs on Platelets: Current Knowledge, Limitations, and Future Perspectives.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely utilized pharmaceuticals worldwide. Besides their recognized anti-inflammatory effects, these drugs exhibit various other pleiotropic effects in several cells, including platelets. Within this article, the multifaceted properties of NSAIDs on platelet functions, activation and viability, as well as their interaction(s) with established antiplatelet medications, by hindering several platelet agonists' pathways and receptors, are thoroughly reviewed. The efficacy and safety of NSAIDs as adjunctive therapies for conditions involving inflammation and platelet activation are also discussed. Emphasis is given to the antiplatelet potential of commonly administered NSAIDs medications, such as ibuprofen, diclofenac, naproxen and ketoprofen, alongside non-opioid analgesic and antipyretic medications like paracetamol. This article delves into their mechanisms of action against different pathways of platelet activation, aggregation and overall platelet functions, highlighting additional health-promoting properties of these anti-inflammatory and analgesic agents, without neglecting the induced by these drugs' side-effects on platelets' functionality and thrombocytopenia. Environmental issues emerging from the ever-increased subscription of these drugs are also discussed, along with the need for novel water treatment methodologies for their appropriate elimination from water and wastewater samples. Despite being efficiently eliminated during wastewater treatment processes on occasion, NSAIDs remain prevalent and are found at significant concentrations in water bodies that receive effluents from wastewater treatment plants (WWTPs), since there is no one-size-fits-all solution for removing all contaminants from wastewater, depending on the specific characteristics of the wastewater. Several novel methods have been studied, with adsorption being proposed as a cost-effective and environmentally friendly method for wastewater purification from such drugs. This article also presents limitations and future prospects regarding the observed antiplatelet effects of NSAIDs, as well as the potential of novel derivatives of these compounds, with benefits in other important platelet functions.

Design, Synthesis, In vitro and In vivo Evaluation of New Imidazo[1,2-a]pyridine Derivatives as Cyclooxygenase-2 Inhibitors.

Cyclooxygenase-2 (COX-2), the key enzyme in the arachidonic acid conversion to prostaglandins, is one of the enzymes associated with different pathophysiological conditions, such as inflammation, cancers, Alzheimer's, and Parkinson's disease. Therefore, COX-2 inhibitors have emerged as potential therapeutic agents in these diseases. The objective of this study was to design and synthesize novel imidazo[1,2-a]pyridine derivatives utilizing rational design methods with the specific aim of developing new potent COX-2 inhibitors. Additionally, we sought to investigate the biological activities of these compounds, focusing on their COX-2 inhibitory effects, analgesic activity, and antiplatelet potential. We aimed to contribute to the development of selective COX-2 inhibitors with enhanced therapeutic benefits. Docking investigations were carried out using AutoDock Vina software to analyze the interaction of designed compounds. A total of 15 synthesized derivatives were obtained through a series of five reaction steps. The COX-2 inhibitory activities were assessed using the fluorescent Cayman kit, while analgesic effects were determined through writing tests, and Born's method was employed to evaluate antiplatelet activities. The findings indicated that the majority of the tested compounds exhibited significant and specific inhibitory effects on COX-2, with a selectivity index ranging from 51.3 to 897.1 and IC50 values of 0.13 to 0.05 μM. Among the studied compounds, derivatives 5e, 5f, and 5j demonstrated the highest potency with IC50 value of 0.05 μM, while compound 5i exhibited the highest selectivity with a selectivity index of 897.19. In vivo analgesic activity of the most potent COX-2 inhibitors revealed that 3-(4-chlorophenoxy)-2-[4-(methylsulfonyl) phenyl] imidazo[1,2-a]pyridine (5j) possessed the most notable analgesic activity with ED50 value of 12.38 mg/kg. Moreover, evaluating the antiplatelet activity showed compound 5a as the most potent for inhibiting arachidonic acidinduced platelet aggregation. In molecular modeling studies, methylsulfonyl pharmacophore was found to be inserted in the secondary pocket of the COX-2 active site, where it formed hydrogen bonds with Arg-513 and His-90. The majority of the compounds examined demonstrated selectivity and potency as inhibitors of COX-2. Furthermore, the analgesic effects observed of potent compounds can be attributed to the inhibition of the cyclooxygenase enzyme.

Discovery of 2,3-Dihydro[1,4]dioxino[2,3-g]benzofuran Derivatives as Protease Activated Receptor 4 (PAR4) Antagonists with Potent Antiplatelet Aggregation Activity and Low Bleeding Tendency.

Patients with arterial embolic disease have benefited greatly from antiplatelet therapy. However, hemorrhage risk of antiplatelet agents cannot be ignored. Herein, we describe the discovery of 2,3-dihydro[1,4]dioxino[2,3-g]benzofuran compounds as novel PAR4 antagonists. Notably, the isomers 36 and 37 with the chemotype of phenoxyl methylene substituted on the 2,3-dihydro-1,4-dioxine ring exhibited potent in vitro antiplatelet activity (IC50 = 26.13 nM for 36 and 14.26 nM for 37) and significantly improved metabolic stability in human liver microsomes (T1/2 = 97.6 min for 36 and 11.1 min for BMS-986120). 36 also displayed good oral PK profiles (mice: T1/2 = 7.32 h and F = 45.11%). Both of them showed overall potent ex vivo antiplatelet activity at concentrations of 6 and 12 mg/kg, with no impact on the coagulation system and low bleeding liability. Our work will facilitate development of novel PAR4 antagonists as a safer therapeutic option for arterial embolism.

TCT-529 Potent Antiplatelet Inhibition Using Ticagrelor Compared to Clopidogrel in Patients Undergoing Drug-Coated Balloon Angioplasty for De Novo Native Coronary Artery Disease

TCT-529 Potent Antiplatelet Inhibition Using Ticagrelor Compared to Clopidogrel in Patients Undergoing Drug-Coated Balloon Angioplasty for De Novo Native Coronary Artery Disease

PB0735 Novel Synthetic Nilotinib Analogues with Improved Cytostatic Properties and Potent Antiplatelet Activity

PB0735 Novel Synthetic Nilotinib Analogues with Improved Cytostatic Properties and Potent Antiplatelet Activity

Synthesis and Evaluation of Novel Nitric Oxide-Donating Ligustrazine Derivatives as Potent Antiplatelet Aggregation Agents.

Antiplatelet aggregation agents have demonstrated clinical benefits in the treatment of ischemic stroke. In our study, a series of novel nitric oxide (NO)-donating ligustrazine derivatives were designed and synthesized as antiplatelet aggregation agents. They were evaluated for the inhibitory effect on 5'-diphosphate (ADP)-induced and arachidonic acid (AA)-induced platelet aggregation in vitro. The results showed that compound 15d displayed the best activity in both ADP-induced and AA-induced assays, and compound 14a also showed quite better activity than ligustrazine. The preliminary structure-activity relationships of these novel NO-donating ligustrazine derivatives were discussed. Moreover, these compounds were docked with the thromboxane A2 receptor to study the structure-activity relationships. These results suggested that the novel NO-donating ligustrazine derivatives 14a and 15d deserve further study as potent antiplatelet aggregation agents.

The changes of blood platelet reactivity in the presence of Elaeagnus rhamnoides (L.) A. Nelson leaves and twig extract in whole blood

Uncontrolled blood platelet activation is an important risk factor of cardiovascular disease (CVDs). Various studies on phenolic compounds indicate that they have a protective effect on the cardiovascular system through different mechanisms, including the reduction of blood platelet activation. One of the plants that is particularly rich in phenolic compounds is sea buckthorn (Elaeagnus rhamnoides (L.) A. Nelson). The aim of the present study in vitro was to determine the anti-platelet properties of crude extracts isolated from leaves and twigs of E. rhamnoides (L.) A. Nelson in whole blood using flow cytometric and total thrombus-formation analysis system (T-TAS). In addition, the aim of our study was also analyze of blood platelet proteomes in the presence of different sea buckthorn extracts. A significant new finding is a decrease surface exposition of P-selectin on blood platelets stimulated by 10 µM ADP and 10 µg/mL collagen, and a decrease surface exposition of GPIIb/IIIa active complex on non-activated platelets and platelets stimulated by 10 µM ADP and 10 µg/mL collagen in the presence of sea buckthorn leaf extract (especially at the concentration 50 µg/mL). The twig extract also displayed antiplatelet potential. However, this activity was higher in the leaf extract than in the twig extract in whole blood. In addition, our present findings clearly demonstrate that investigated plant extracts have anticoagulant properties (measured by T-TAS). Therefore, the two tested extracts may be promising candidates for the natural anti-platelet and anticoagulant supplements.

The State of the Haemostasis System under Conditions of Immobilization Stress against the Background of Experimental Metabolic Syndrome

The state of the haemostasis system under conditions of immobilization stress against the background of metabolic syndrome (MS) in male Wistar rats was studied. Two series of experiments were conducted using single and multiple immobilization effects. It was shown that the development of MS with prolonged maintenance of rats on a high-calorie diet led to a decrease in anticoagulant-fibrinolytic and antiplatelet potential of blood. In the plasma of intact rats subjected to both single and multiple immobilization, an increase in blood clotting and a decrease in fibrinolysis were found. At the same time, the use of multiple immobilization effects in comparison with single immobilization contributed to a more pronounced increase in platelet aggregation. The combination of both single and multiple immobilization and MS in rats caused a significant decrease in fibrinolysis, anticoagulant activity of blood and increased platelet aggregation. However, in the case of repeated immobilization exposure, an even more significant increase in ADP-dependent platelet aggregation was observed. A comparative analysis of the indicators of primary and plasma haemostasis under these experimental conditions allows us to conclude that immobilization, regardless of its duration, aggravates the state of hypercoagulation in rats with MS. Moreover, repeated immobilization stress on the background of metabolic disorders leads to more pronounced hypercoagulation shifts due to an increase in platelet aggregation by 2 times compared with intact animals.

The Antiplatelet Effect of 4-Methylcatechol in a Real Population Sample and Determination of the Mechanism of Action.

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.

Antiplatelet activity of Lampaya medicinalis Phil. in human platelets

Herbal preparations can have beneficial effects to counteract cardiovascular diseases (CVD). Inhibition of platelet aggregation have been shown to be effective in CVD treatment. Medicinal plants contain beneficial compounds that could be a useful source of dietary phytochemicals. In this study, it was evaluated whether the hydroethanolic extract of Lampaya medicinalis Phil. (HEL) and two of its components, genipin and picein, are capable of reducing human platelet aggregation and whether such effect could be associated with the reduction of platelet activation markers. HEL significantly inhibited platelet aggregation stimulated with ADP and TRAP-6 (58 and 80%, respectively). The antiplatelet potential of HEL was reached from 250 μg/mL and at 1000 μg/mL when TRAP-6 and ADP, respectively, were used as agonist. The extract also inhibited GPIIb/IIIa activation at the highest concentration tested (1000 μg/mL). On the other hand, genipin at 20 μM significantly reduced P-selectin expression and GPIIb/IIIa activation, while picein decreased P-selectin expression as well as GPIIb/IIIa activation at 10 μM and 50 μM, respectively. Lampaya medicinalis Phil. might be a good candidate for cardiovascular protection, however further studies are needed to elucidate the mechanism by which this extract inhibits antiplatelet activity.

Participation of Nitric Oxide in the Realization of Hemostatic Effects of Glyproline Peptides.

The involvement of nitric oxide in the responses of the hemostasis system to the appearance of proline-containing peptides in the blood was studied in experiments on rats. It was shown that a single intranasal administration of peptides PGP, RPGP, and PGPL to rats led to an increase in fibrinolytic, anticoagulant, and antiplatelet potential of blood. The use of the non-selective NO-synthase blocker L-NAME almost completely inhibited the anticoagulant effects of the glyprolines. It was found that the mechanism of the anticoagulant-fibrinolytic and antiplatelet action of glyproline peptides is determined by the activation of the enzymatic pathway of nitric oxide formation. The obtained results revealed the involvement of nitric oxide in the implementation of hemostatic and vascular-endothelial functions of the organism.

A Comprehensive Literature Review on Cardioprotective Effects of Bioactive Compounds Present in Fruits of Aristotelia chilensis Stuntz (Maqui).

Some fruits and vegetables, rich in bioactive compounds such as polyphenols, flavonoids, and anthocyanins, may inhibit platelet activation pathways and therefore reduce the risk of suffering from CVD when consumed regularly. Aristotelia chilensis Stuntz (Maqui) is a shrub or tree native to Chile with outstanding antioxidant activity, associated with its high content in anthocyanins, polyphenols, and flavonoids. Previous studies reveal different pharmacological properties for this berry, but its cardioprotective potential has been little studied. Despite having an abundant composition, and being rich in bioactive products with an antiplatelet role, there are few studies linking this berry with antiplatelet activity. This review summarizes and discusses relevant information on the cardioprotective potential of Maqui, based on its composition of bioactive compounds, mainly as a nutraceutical antiplatelet agent. Articles published between 2000 and 2022 in the following bibliographic databases were selected: PubMed, ScienceDirect, and Google Scholar. Our search revealed that Maqui is a promising cardiovascular target since extracts from this berry have direct effects on the reduction in cardiovascular risk factors (glucose index, obesity, diabetes, among others). Although studies on antiplatelet activity in this fruit are recent, its rich chemical composition clearly shows that the presence of chemical compounds (anthocyanins, flavonoids, phenolic acids, among others) with high antiplatelet potential can provide this berry with antiplatelet properties. These bioactive compounds have antiplatelet effects with multiple targets in the platelet, particularly, they have been related to the inhibition of thromboxane, thrombin, ADP, and GPVI receptors, or through the pathways by which these receptors stimulate platelet aggregation. Detailed studies are needed to clarify this gap in the literature, as well as to specifically evaluate the mechanism of action of Maqui extracts, due to the presence of phenolic compounds.

Clinical outcomes with the use of ticagrelor or clopidogrel after fibrinolytic therapy in patients with ST-elevation myocardial infarction – A prospective observational study

Background: Thrombolytic therapy in the appropriate window period remains the most commonly used therapy in ST-elevation myocardial infarction patients, despite the advantage of primary percutaneous coronary intervention (PCI) over it. Use of newer more potent antiplatelets agents early after thrombolysis carries the chance of increasing bleeding complications, thus we planned to have a study to assess the safety and efficacy of ticagrelor as compared to clopidogrel in thrombolysed patients. Materials and Methods: This was a prospective observational study in Indian patients. A total of 142 patients were enrolled in the study with 76 in the ticagrelor group and 66 in the clopidogrel group. All patients received thrombolysis as the primary reperfusion strategy. Patients receiving either clopidogrel or ticagrelor after thrombolysis irrespective of the subsequent PCI status were followed up for any bleeding events (primary endpoints) as per thrombolysis in myocardial infarction (TIMI) definition and Bleeding Academic Research Consortium (BARC) definition. Major adverse cardiac events (MACE) including death from cardiovascular causes, myocardial infarction (MI), and stroke were also assessed as markers of efficacy and secondary endpoints. Results: Mean time from thrombolysis to study drug use was 18.9 ± 2.1 h in the ticagrelor group as compared to 14.8 ± 3.3 h in the clopidogrel group (P > 0.05). For major bleeding events (TIMI major), no statistically significant difference was observed between groups (2.6% in ticagrelor vs. 1.5% in clopidogrel) (P = 0.6). BARC 3–5 bleeding at 1-month follow-up was significantly higher in the ticagrelor group compared to the clopidogrel group (P = 0.04). At 1-month follow-up, BARC 1–2 or 3–5 bleeding events in the subjects who underwent PCI were higher in the ticagrelor group than the clopidogrel group (P = 0.03). Patients in the clopidogrel group have more major adverse cardiac events than the ticagrelor group especially driven by more fatal and nonfatal MI in the clopidogrel group (P = 0.04). Conclusions: Ticagrelor can be safely administered in postthrombolytic patients similar to clopidogrel albeit at the cost of slightly increased minor bleeding events in short-term follow-up.

Antiplatelet and Anticoagulant Activity of Isorhamnetin and Its Derivatives Isolated from Sea Buckthorn Berries, Measured in Whole Blood.

Blood platelets play a crucial role in hemostasis, the process responsible for keeping blood flowing in the circulatory system. However, unnecessary platelet activation can lead to aggregation at the site of atherosclerotic plaque rapture and the formation of a thrombus, which promotes atherothrombotic diseases. Various dietary components, such as phenolic compounds, are known to demonstrate antiplatelet and anticoagulant properties, and it is possible that these could form an important element in the prophylaxis and therapy of cardiovascular diseases. Our present study examined the biological activity of isorhamnetin (1) and two isorhamnetin derivatives, (2): 3-O-beta-glucoside-7-O-alpha-rhamnoside and (3): 3-O-beta-glucoside-7-O-alpha-(3″′-isovaleryl)-rhamnoside, isolated from the phenolic fraction of sea buckthorn fruit, against human washed blood platelets and human whole blood in vitro. The anti-platelet and anticoagulant potential was determined using (A) flow cytometry, (B) the thrombus-formation analysis system (T-TAS) and (C) colorimetry. The results of the T-TAS test indicate that the AUC10 (Area Under the Curve) of the tested phenolic compounds (compounds 1, 2 and 3; 50 µg/mL) was markedly reduced compared to the control values. Moreover, flavonol demonstrated anti-platelet potential, including anti-adhesive activity, with these effects being more intense in compound 2 than isorhamnetin. Different actions of flavonol on platelet activation may depend on their binding ability to various receptors on blood platelets. However, the mechanism of their anti-platelet potential requires further additional studies, including in vitro and in vivo experiments.

Antioxidant Capacity and Antiplatelet Activity of Aqueous Extracts of Common Bean (Phaseolus vulgaris L.) Obtained with Microwave and Ultrasound Assisted Extraction.

Phaseolus vulgaris L. has beneficial effects on several chronic non-communicable diseases (e.g., cardiovascular diseases) related to oxidative stress. This redox state may influence platelet activation and aggregation; which is crucial in thrombus formation. In this work, the antiplatelet and antioxidant potential of aqueous extracts obtained by green processes, microwave-assisted extraction and ultrasound-assisted extraction, from 25 landraces of common beans were investigated. Phenol content and antioxidant potential were determined using the Folin-Ciocalteu method, total monomeric anthocyanin and ORAC assay, respectively. The antiplatelet potential of the extracts was explored by turbidimetry. Microwave extraction showed higher phenol content and antioxidant activity in most extracts. Soja landrace extract obtained by microwave-assisted extraction showed higher phenol content and antioxidant activity (893.45 ± 87.30 mg GAE/g and 35,642.85 ± 2588.88 ORAC μmolTE/g, respectively). Although most of the extracts obtained by microwave-assisted extraction showed antiplatelet activity, the extract of Hallado Aleman landrace obtained by ultrasound-assisted extraction (IC50 = 0.152 ± 0.018 mg/mL) had the highest antiplatelet potential. The extraction method, MAE and UAE, influences the biological potential of the beans, specifically the antiplatelet activity and antioxidant activity. The functional value of this legume for direct consumption by the population was evidenced, as well as its inclusion in food formulations.

In-Hospital Bleeding in Elderly Patients With Acute Coronary Syndrome: Are Potent Antiplatelet Agents Safe?

Despite implementation of new interventional techniques and therapeutic advances, elderly patients with acute coronary syndrome (ACS) continue to be susceptible to in-hospital bleeding compared with younger ones. Thus, we investigated the incidence of in-hospital bleeding events and associated risk factors in elderly (≥ 75°years) ACS patients. We also wanted to define the bleeding sites, characteristics, and associated mortality. Bleeding Academic Research Consortium (BARC) classification type 2, 3, or 5 was used to define bleeding events. Overall, 539 patients were included in the study (mean age: 82.5 ± 4.8°years; 282 (52.3%) females). Of these patients, 69 (12.8%) developed in-hospital bleeding. Factors that were independently related with in-hospital bleeding were age (odds ratio (OR): 1.08; 95% confidence interval (CI): 1.011.14, P = .01), acute kidney injury (OR: 3.66; 95% CI: 2.016.69; P < .01), tirofiban (OR: 4.43; 95% CI: 1.7810.99; P < .01), and ticagrelor (OR: 1.93; 95% CI: 1.013.73; P = .04) administration. The urinary tract was the most frequent bleeding site, followed by femoral arteries. In conclusion, ticagrelor and tirofiban should be used with caution in elderly ACS patients.

Potent antiplatelet aggregation, anticoagulant and antioxidant activity of aerial Canna x generalis L.H Bailey & E.Z Bailey and its phytoconstituents

This study evaluated for the first time the inhibitory effect on human platelet aggregation, blood coagulation, and the antioxidant activity of Canna x generalis fractions and its phytoconstituents. The antiplatelet effect was evaluated using the turbidimetric method to determine the percentage inhibition (%I), the area under aggregation curve (AUC) and the aggregation velocity (slope). Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) were measured to assess the inhibitory effect on blood coagulation. ABTS and DPPH assays were performed for evaluation of the antioxidant effect. Compounds structures were determined by NMR and MS spectroscopic methods. The ethyl acetate fraction exhibited the most potent antiplatelet (%I, 98.2 ± 1.7% at 4 mg/mL), anticoagulation (mean APTT, 42.97 s) and antioxidant activity (IC50, 58 ± 0.1 and 12.5 ± 2.0 μg/mL for DPPH and ABTS, respectively). Thirteen compounds were found for the first time from aerial CG: 16α-hydro‑ent-kauran-3β-ol-7,19-dioic acid, named cannagelic acid (a new ent‑kaurane diterpenoid) (1), 16α-hydro‑ent-kauran-17,19-dioic acid (2), ent‑kauran-15-en-17,19-dioic acid (3), 3-methoxybenzaldehyde (4), 2-methoxynaphtalene (5), 4-ketopinoresinol (6), p-coumaric acid (7), indole-3-carboxylic acid (8), procatechuic aldehyde (9), astragalin (10), isoquercitrin (11), corchoionol C (12) and rutin (13). Compounds 7, 9–11, 13 possess good antiplatelet, anticoagulant and antioxidant activity. This study demonstrated that compound 1 did not show any tested effects. Compounds 4 and 5 had a very weak antiplatelet effect. Compound 8 expressed the highest capacity to inhibit platelet aggregation for both ADP and collagen (%I = 70.2 ± 1.8 and 79.2 ± 1.4 at 0.4 mg/mL, respectively), followed by compound 6. Moreover, these two compounds at 0.4 mg/mL could prolong APTT compared to the negative control (p < 0.05). Compound 12 had weak antiplatelet activity, but its antioxidant effect was better than other tested compounds. In conclusion, CG would be a good natural resource of bioactive molecules or dietary supplements to prevent and/or treat cardiovascular and free radicals-associated diseases.