ReferenceID 5537

Juglone prevents human platelet aggregation through inhibiting Akt and protein disulfide isomerase

Phytomedicine

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

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Reference Id
5537
Evidence Id
22127
Core Evidence Id
22127
Source Reference Id
4305
Herb2 Reference Id
HBREF005102
Subject Paper Key
HBIN031581_33387969
Pubmed Id
33387969
Doi
10.1016/j.phymed.2020.153449
Paper Title
Juglone prevents human platelet aggregation through inhibiting Akt and protein disulfide isomerase
Paper Abstract
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 muM) 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 Ca2+ 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.
Journal
Phytomedicine
Publish Year
2021
Experiment Subject
human; juglone-treated platelets
Experiment Type
Cell Experiment
Phenotype Related
Diabetic Vascular Complications; Cancer; Inflammation
Paper Title Cn
Paper Title En
Juglone prevents human platelet aggregation through inhibiting Akt and protein disulfide isomerase
Bilingual Status
semi_complete