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

Phytomedicine

Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan; Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Electronic address:

Published: February 2021

AI Article Synopsis

  • Juglone, a natural compound found in certain plants, is being explored as a potential treatment for cancer, inflammation, and diabetes-related vascular issues, with its antiplatelet effects studied for the first time here.
  • The study utilized various lab techniques, including aggregometry and flow cytometry, to analyze juglone's impact on human platelet function and its effects on thrombus formation under blood flow conditions.
  • Results showed that juglone effectively inhibited platelet aggregation, reduced thrombus formation, and impacted specific cellular signaling pathways, highlighting its potential as an antiplatelet and antithrombotic agent.

Article 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 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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Source
http://dx.doi.org/10.1016/j.phymed.2020.153449DOI Listing

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