Background/purpose: Juglone, a natural compound widely found in Juglandaceae plants, has been suggested as a potential drug candidate for treating cancer, inflammation, and diabetic vascular complications. In the present study, the antiplatelet effect and underlying mechanisms of juglone were investigated for the first time.
Study Design/methods: Human platelet aggregation and activation were measured by turbidimetric aggregometry, flow cytometry, and Western blotting. In vitro antithrombotic activity of juglone was assessed using collagen-coated flow chambers under whole-blood flow conditions. The effect of juglone on protein disulfide isomerase (PDI) activity was determined by the dieosin glutathione disulfide assay.
Results: Juglone (1 - 5 μM) inhibited platelet aggregation and glycoprotein (GP) IIb/IIIa activation caused by various agonists. In a whole blood flow chamber system, juglone reduced thrombus formation on collagen-coated surfaces under arterial shear rates. Juglone abolished intracellular Ca elevation and protein kinase C activation caused by collagen, but had no significant effect on that induced by G protein-coupled receptor agonists. In contrast, Akt activation caused by various agonists were inhibited in juglone-treated platelets. Additionally, juglone showed inhibitory effects on both recombinant human PDI and platelet surface PDI at concentrations similar to those needed to prevent platelet aggregation.
Conclusion: Juglone exhibits potent in vitro antiplatelet and antithrombotic effects that are associated with inhibition of Akt activation and platelet surface PDI activity.
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http://dx.doi.org/10.1016/j.phymed.2020.153449 | DOI Listing |
Biochimie
January 2025
Laboratory of Applied Toxinology, Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Butantan Institute, São Paulo, Brazil. Electronic address:
PA-BJ is a serine protease present in Bothrops jararaca venom that triggers platelet aggregation and granule secretion by activating the protease-activated receptors PAR-1 and PAR-4, without clotting fibrinogen. These receptors also have a relevant role in endothelial cells, however, the interaction of PA-BJ with other membrane-bound or soluble targets is not known. Here we explored the activity of PA-BJ on endothelial cell receptor, cytoskeleton, and coagulation proteins in vitro, and show the degradation of fibrinogen and protein C, and the limited proteolysis of actin, EPCR, PAR-1, and thrombomodulin.
View Article and Find Full Text PDFSci Rep
January 2025
Gachon Medical Research Institute, Gachon Biomedical Convergence Institute, Gachon University Gil Medical Center, College of Medicine, Gachon University, Incheon, 21565, Republic of Korea.
The benefit of aspirin in primary prevention for atherosclerotic cardiovascular diseases (ASCVD) is questionable due to bleeding complications. We analyzed the Korean National Health Insurance data to compare the efficacy and overall bleeding of sarpogrelate, an antiplatelet agent with lower bleeding risk, versus aspirin in high-/very-high-risk diabetic populations without prior ASCVD. The primary endpoint was net adverse clinical events (NACE), defined as a composite of efficacy and overall bleeding.
View Article and Find Full Text PDFOpen Heart
January 2025
Cardiology, Radboudumc, Nijmegen, The Netherlands
Background And Aims: Due to the multitude of risk factors outlined in the guidelines, personalised dual antiplatelet therapy (DAPT) guidance after percutaneous coronary intervention (PCI) is complex. A simplified method was created to facilitate the use of risk stratification. We aimed to compare the predictive and prognostic value of the 'Zuidoost Nederland Hart Registratie' (ZON-HR) classification for bleeding risk with the PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent DAPT (PRECISE-DAPT) score and to determine the effect of ticagrelor monotherapy versus DAPT in patients with or without high bleeding risk (HBR).
View Article and Find Full Text PDFNeurosurg Rev
January 2025
Neurosurgery Center, Department of Cerebrovascular Surgery, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Ticagrelor has become the standard drug for the treatment of intracranial aneurysms (IAs) with flow diverters (FDs), but the dosage has not been standardized. The effect of platelet function on clinical and imaging prognosis remains unclear. This study aimed to show the effects of different doses of ticagrelor and platelet aggregation function on the clinical and imaging prognosis after FDs treatment of aneurysms.
View Article and Find Full Text PDFMicrosurgery
January 2025
Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Background: Acetylsalicylic acid (ASA) has been used in reconstructive microsurgery since the inception of the field. However, when compared to placebo groups, its efficacy is not confirmed. In our study, we hypothesize that the utility of ASA postoperatively in microvascular surgery is not associated with improved outcomes.
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