期刊
PHYTOMEDICINE
卷 82, 期 -, 页码 -出版社
ELSEVIER GMBH
DOI: 10.1016/j.phymed.2020.153449
关键词
Juglone; Akt; Protein disulfide isomerase; Platelet aggregation; Thrombosis
资金
- Ministry of Science and Technology, Taiwan [MOST106-2320-B-037-003-MY3]
- Kaohsiung Medical University, Taiwan [KMU-TC108A03-4, KMU-DK109002-4]
Juglone demonstrates potent in vitro antiplatelet and antithrombotic effects, associated with the inhibition of Akt activation and platelet surface PDI activity.
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 mu M) 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据