Novel Antiplatelet Activity of Ginsenoside Re Through the Inhibition of High Shear Stress-Induced Platelet Aggregation

作者全名："Huang, Xiaojing; Zhang, Tiancong; Gao, Xuemei; Huan, Xuanrong; Li, Yuan"

作者地址："[Huang, Xiaojing; Zhang, Tiancong; Gao, Xuemei; Huan, Xuanrong; Li, Yuan] Chongqing Med Univ, Yongchuan Hosp, Cent Lab, Chongqing, Peoples R China; [Li, Yuan] Chongqing Med Univ, Yongchuan Hosp, Cent Lab, 439,Xuanhua Rd, Chongqing 402160, Peoples R China"

通信作者："Li, Y (通讯作者)，Chongqing Med Univ, Yongchuan Hosp, Cent Lab, 439,Xuanhua Rd, Chongqing 402160, Peoples R China."

来源：JOURNAL OF CARDIOVASCULAR PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001024602300006

JCR分区：Q2

影响因子：2.6

年份：2023

卷号：82

期号：1

开始页：40

结束页：51

文献类型：Article

关键词：ginsenoside re; shear stress; antiplatelet

摘要："Bleeding is one of the most serious side effects of antiplatelet drugs. Efforts have been made to find new antiplatelet agents without bleeding complications. Shear-induced platelet aggregation (SIPA) occurs only under pathological conditions and is a promising target for overcoming bleeding problems. This work demonstrates that the ginsenoside Re selectively inhibits platelet aggregation induced by high shear stress. Human platelets were exposed to high shear stress using microfluidic chip technology, and aggregation, activation, and phosphatidylserine (PS) exposure were measured. The Von Willebrand Ristocetin Cofactor (vWF:RCo) assay and western blot were used to evaluate the effect of the vWF-GPIb/PI3K/Akt signal pathway. The coagulation and bleeding risk were evaluated by measuring the coagulation parameters PT, APTT, TT, and thromboelastography. The 3-dimensional morphology of platelet aggregates was observed by a microscopic 3-dimensional imaging. Re was a potent inhibitor of SIPA, with an IC50 of 0.071 mg/mL. It effectively blocked shear stress-induced platelet activation without any significant toxicity. It was highly selective against SIPA, effectively inhibiting vWF-GPIb and the downstream PI3K/Akt signaling pathway. Most importantly, Re did not affect normal blood coagulation and did not increase the risk of bleeding. In conclusion, Re inhibits platelet activation through the inhibition of the vWF-GPIb/PI3K/Akt pathway. Thus, it might be considered as a new antiplatelet drug in the prevention of thrombosis without increasing the risk of bleeding."

基金机构：National Natural Sciences Foundation of China [11702047]; Special Project of Science and Technology Innovation for People's Livelihood Security of Chongqing [cstc2017shmsA130009]; Chongqing Medical Research Program [2017MSXM079]; Postdoctoral Research Project of Chongqing [Xm2017082]; Postgraduate Innovation Fund of Yongchuan Hospital Affiliated to Chongqing Medical University [YJSCX202202]; Joint Project of Chongqing Health Commission; Science and Technology Bureau [2023GDRC008]

基金资助正文："This work was supported by the National Natural Sciences Foundation of China (11702047), the Special Project of Science and Technology Innovation for People's Livelihood Security of Chongqing(cstc2017shmsA130009), the Chongqing Medical Research Program(2017MSXM079), the Postdoctoral Research Project of Chongqing(Xm2017082), the Postgraduate Innovation Fund of Yongchuan Hospital Affiliated to Chongqing Medical University (YJSCX202202)and the Joint Project of Chongqing Health Commission and Science and Technology Bureau (2023GDRC008)"