Novel Antiplatelet Activity of Ginsenoside Re Through the Inhibition of High Shear Stress-Induced Platelet Aggregation.
Humans
Platelet Aggregation
von Willebrand Factor
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Phosphatidylinositol 3-Kinases
/ metabolism
Blood Platelets
Platelet Aggregation Inhibitors
/ adverse effects
Hemorrhage
/ chemically induced
Stress, Mechanical
Platelet Glycoprotein GPIb-IX Complex
/ adverse effects
Journal
Journal of cardiovascular pharmacology
ISSN: 1533-4023
Titre abrégé: J Cardiovasc Pharmacol
Pays: United States
ID NLM: 7902492
Informations de publication
Date de publication:
01 Jul 2023
01 Jul 2023
Historique:
received:
22
11
2022
accepted:
24
02
2023
medline:
10
7
2023
pubmed:
10
3
2023
entrez:
9
3
2023
Statut:
epublish
Résumé
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 IC 50 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.
Identifiants
pubmed: 36892287
doi: 10.1097/FJC.0000000000001417
pii: 00005344-202307000-00006
doi:
Substances chimiques
von Willebrand Factor
0
ginsenoside Re
46F3R0BL3I
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
Platelet Aggregation Inhibitors
0
Platelet Glycoprotein GPIb-IX Complex
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
40-51Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest.
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