Isorhynchophylline Inhibits Platelet Activation and Thrombus Formation.

IF 2.6 4区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Yun Liu, Hui Zhu, Yue Dai, Jie Zhang, Yingying Li, Huimin Jiang, Yueyue Sun, Jianlin Qiao, Xiaoqi Xu
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引用次数: 0

Abstract

Abstract: Isorhynchophylline is a Chinese herbal medicine and has multiple effects such as anti-inflammatory and neuroprotective effects. Whether isorhynchophylline has antithrombotic property is unknown. This study aims to evaluate its role in platelet function. Human platelets were incubated with isorhynchophylline (0, 10, 20, and 40 μM) at 37°C for 1 hour to detect platelet aggregation and activation, receptors level, spreading, and calcium mobilization. In addition, isorhynchophylline (5 mg/kg) was injected into mice to measure in vivo hemostasis and thrombosis. Isorhynchophylline dose-dependently reduced platelet aggregation, adenosine triphosphate secretion, P-selectin expression, and α IIb β 3 activation induced by collagen-related peptide or thrombin without affecting surface level of receptors α IIb β 3 , GPIbα, and glycoprotein VI. Meanwhile, isorhynchophylline-treated platelets showed reduced spreading. Moreover, isorhynchophylline reduced platelet calcium mobilization, phosphatidylserine exposure, and the phosphorylation of PLCγ2 and PKCα. Furthermore, administration of isorhynchophylline into mice impaired platelet hemostatic function and arterial/venous thrombosis without affecting coagulation. In conclusion, isorhynchophylline impairs platelet function and arterial/venous thrombosis, implying its potential to be a novel agent for treating thrombotic or cardiovascular diseases.

异蛇碱抑制血小板活化和血栓形成。
异蛇碱是一种中草药,具有抗炎、神经保护等多种作用。异蛇碱是否具有抗血栓特性尚不清楚。本研究旨在评价其在血小板功能中的作用。人血小板与异羟基苯甲酸(0、10、20和40 μM)在37℃下孵育1小时,检测血小板聚集和活化、受体水平、扩散和钙动员。另外,小鼠体内注射异蛇碱(5 mg/kg),观察小鼠体内止血和血栓形成情况。异酸碱剂量依赖性地降低胶原相关肽(CRP)或凝血酶诱导的血小板聚集、ATP分泌、p -选择素表达和α ib β3活化,而不影响受体α ib β3、GPIbα和GPVI的表面水平。与此同时,异氰酸钠处理的血小板显示出减少扩散。此外,异酸碱还能降低血小板钙动员、磷脂酰丝氨酸暴露和plc - γ - 2和pkc - α的磷酸化。此外,异蛇碱给药小鼠可损害血小板止血功能和动脉/静脉血栓形成,但不影响凝血。综上所述,异氢茶碱可损害血小板功能和动脉/静脉血栓形成,这意味着它有可能成为治疗血栓性或心血管疾病的新药物。
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来源期刊
CiteScore
5.10
自引率
3.30%
发文量
367
审稿时长
1 months
期刊介绍: Journal of Cardiovascular Pharmacology is a peer reviewed, multidisciplinary journal that publishes original articles and pertinent review articles on basic and clinical aspects of cardiovascular pharmacology. The Journal encourages submission in all aspects of cardiovascular pharmacology/medicine including, but not limited to: stroke, kidney disease, lipid disorders, diabetes, systemic and pulmonary hypertension, cancer angiogenesis, neural and hormonal control of the circulation, sepsis, neurodegenerative diseases with a vascular component, cardiac and vascular remodeling, heart failure, angina, anticoagulants/antiplatelet agents, drugs/agents that affect vascular smooth muscle, and arrhythmias. Appropriate subjects include new drug development and evaluation, physiological and pharmacological bases of drug action, metabolism, drug interactions and side effects, application of drugs to gain novel insights into physiology or pathological conditions, clinical results with new and established agents, and novel methods. The focus is on pharmacology in its broadest applications, incorporating not only traditional approaches, but new approaches to the development of pharmacological agents and the prevention and treatment of cardiovascular diseases. Please note that JCVP does not publish work based on biological extracts of mixed and uncertain chemical composition or unknown concentration.
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