Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan.
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Family Medicine, Pingtung Hospital, Ministry of Health and Welfare, Pingtung, Taiwan.
Phytomedicine. 2021 Feb;82:153449. doi: 10.1016/j.phymed.2020.153449. Epub 2020 Dec 25.
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.
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.
Juglone exhibits potent in vitro antiplatelet and antithrombotic effects that are associated with inhibition of Akt activation and platelet surface PDI activity.
背景/目的：胡桃醌是一种广泛存在于胡桃科植物中的天然化合物，已被提议作为治疗癌症、炎症和糖尿病血管并发症的潜在药物候选物。在本研究中，首次研究了胡桃醌的抗血小板作用及其机制。
研究设计/方法：通过比浊法聚集仪、流式细胞术和 Western blot 测定人血小板聚集和活化。在全血流动条件下使用胶原涂覆的流动室评估胡桃醌的体外抗血栓形成活性。通过二恶嗪谷胱甘肽二硫化物测定法测定胡桃醌对蛋白二硫键异构酶 (PDI) 活性的影响。
胡桃醌（1-5 μM）抑制了各种激动剂引起的血小板聚集和糖蛋白 (GP) IIb/IIIa 活化。在全血流室系统中，胡桃醌降低了胶原涂覆表面在动脉剪切率下的血栓形成。胡桃醌消除了胶原引起的细胞内 Ca 升高和蛋白激酶 C 活化，但对 G 蛋白偶联受体激动剂引起的活化没有显著影响。相比之下，胡桃醌处理的血小板中各种激动剂诱导的 Akt 活化受到抑制。此外，胡桃醌在抑制重组人 PDI 和血小板表面 PDI 方面均具有抑制作用，其浓度与抑制血小板聚集所需的浓度相似。
胡桃醌具有体外抗血小板和抗血栓形成作用，这与抑制 Akt 活化和血小板表面 PDI 活性有关。
