AUTHOR=Liu Gang , Yuan Zhaowei , Tian Xiaoyun , Xiong Xiuqin , Guo Fang , Lin Zihan , Qin Zhen 

TITLE=Pimpinellin Inhibits Collagen-induced Platelet Aggregation and Activation Through Inhibiting Granule Secretion and PI3K/Akt Pathway

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.706363

DOI=10.3389/fphar.2021.706363

ISSN=1663-9812

ABSTRACT=<p>Pimpinellin is a coumarin-like compound extracted from the root of <italic>Toddalia asiatica</italic>. Its effects on platelet function has not been investigated. This study found that pimpinellin pretreatment effectively inhibited collagen-induced platelet aggregation, but did not alter ADP- and thrombin-induced aggregation. Platelets pretreated with pimpinellin showed reduced α granule (CD62) level and secretion of dense granule (ATP release). Pimpinellin-treated platelets also exhibited decreased clot reaction and TxB2 production. Pimpinellin pretreatment suppressed adhesion and spreading of human platelets on the fibrinogen coated surface. Analysis of tail bleeding time of mice administered with pimpinellin (40 mg/kg) revealed that pimpinellin did not change tail bleeding time significantly, number of blood cells, and APTT and PT levels. Pimpinellin inhibited collagen-induced <italic>ex vivo</italic> aggregation of mice platelets. Immunoblotting results showed that pimpinellin suppressed collagen-induced phosphorylation of PI3K-Akt-Gsk3β and PKC/MAPK in platelets.</p>