The Marine-Derived Triterpenoid Frondoside A Inhibits Thrombus Formation

Marine Drugs

MichaelD. Menger¹  Thomas Später¹  Lisa Nalbach²  MatthiasW. Laschke²  Emmanuel Ampofo² 

[1] Experimental Surgery, Saarland University, 66421 Homburg/Saar, Germany;;Institute for Clinical &

关键词: frondoside a;    thrombus formation;    thrombosis;    hemostasis;    platelets;    pi3k;    dorsal skinfold chamber;   

DOI  :  10.3390/md18020111

来源: DOAJ

【 摘 要 】

Background: The marine-derived triterpenoid frondoside A inhibits the phosphatidylinositol-3-kinase (PI3K) pathway in cancer cells. Because this pathway is also crucially involved in platelet activation, we studied the effect of frondoside A on thrombus formation. Methods: Frondoside A effects on platelet viability, surface adhesion molecule expression, and intracellular signaling were analyzed by flow cytometry and Western blot. The effect of frondoside A was analyzed by photochemically induced thrombus formation in the mouse dorsal skinfold chamber model and by tail vein bleeding. Results: Concentrations of up to 15 µM frondoside A did not affect the viability of platelets, but reduced their surface expression of P-selectin (CD62P) and the activation of glycoprotein (GP)IIb/IIIa after agonist stimulation. Additional mechanistic analyses revealed that this was mediated by downregulation of PI3K-dependent Akt and extracellular-stimuli-responsive kinase (ERK) phosphorylation. Frondoside A significantly prolonged the complete vessel occlusion time in the mouse dorsal skinfold chamber model of photochemically induced thrombus formation and also the tail vein bleeding time when compared to vehicle-treated controls. Conclusion: Our findings demonstrated that frondoside A inhibits agonist-induced CD62P expression and activation of GPIIb/IIIa. Moreover, frondoside A suppresses thrombus formation. Therefore, this marine-derived triterpenoid may serve as a lead compound for the development of novel antithrombotic drugs.

【 授权许可】

Unknown