Antiplatelet Activity of Tussilagone via Inhibition of the GPVI Downstream Signaling Pathway in Platelets

Frontiers in Medicine

article

Jing Zhou¹  Ru-Ping Yang²  Wei Song³  Hui-Min Xu⁴  Yong-Hui Wang¹ 

[1]Department of Pharmacy, Zhumadian Central Hospital

[2]Department of Pharmacy, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science

[3]Department of Pharmacy, Renmin Hospital, Wuhan University

[4]Department of Pharmacy, Second Affiliated Hospital, Zhejiang University School of Medicine

关键词: tussilagone;    sesquiterpenoid;    antiplatelet;    thrombosis;    glycoprotein VI pathway;   

DOI  :  10.3389/fmed.2020.00380

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Tussilagone is a sesquiterpenoid extracted from Tussilago farfara and is used as an oriental medicine for asthma and bronchitis. Although previous studies have shown that tussilagone has an inhibitory effect on platelet aggregation, no studies have been performed to investigate its precise effect on platelets, and the underlying mechanism remains unclear. In the present study, we showed that tussilagone inhibited platelet aggregation induced by collagen, thrombin and ADP, as well as platelet release induced by collagen and thrombin, in mice. Tussilagone decreased P-selectin expression and αIIbβ3 activation (JON/A binding) in activated platelets, which indicated that tussilagone inhibited platelet activation. Moreover, tussilagone suppressed platelet spreading on fibrinogen and clot retraction. The levels of phosphorylated Syk, PLCγ2, Akt, GSK3β, and MAPK (ERK1/2 and P38) and molecules associated with GPVI downstream signaling were downregulated in the presence of tussilagone. In addition, tussilagone prolonged the occlusion time in a mouse model of FeCl 3 -induced carotid artery thrombosis and had no effect on mouse tail bleeding time. These results indicate that tussilagone inhibits platelet function in vitro and in vivo and that the underlying mechanism involves the Syk/PLCγ2-PKC/MAPK and PI3K-Akt-GSK3β signaling pathways downstream of GPVI. This research suggests that tussilagone is a potential candidate antiplatelet drug for the prevention of thrombosis.

【 授权许可】

CC BY