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Novel factor Xa inhibitor, maslinic acid, with antiplatelet aggregation activity
Author(s) -
Kim KyungMin,
Kim Jaehong,
Baek MoonChang,
Bae JongSup
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29749
Subject(s) - antithrombotic , chemistry , pharmacology , adenosine diphosphate , platelet , thromboxane a2 , platelet activation , thrombin , platelet aggregation inhibitor , biochemistry , medicine , aspirin , platelet aggregation , receptor
As antithrombotic effects of maslinic acid (MA) have not yet been studied, MA‐mediated downregulation of coagulation factor Xa (FXa) and platelet aggregation was studied. We show that MA inhibited the enzymatic activity of FXa and platelet aggregation, induced by adenosine diphosphate (ADP) and a thromboxane A 2 (TXA 2 ) analog, U46619 with a similar antithrombotic efficacy to rivaroxaban, a direct FXa inhibitor used as a positive control. Mechanistically, MA suppressed U46619‐ or ADP‐induced phosphorylation of myristoylated alanine‐rich C kinase substrate, and the expression of P‐selectin, and activated PAC‐1 in platelets. MA increased generation of nitric oxide, but downregulated excessive secretion of endothelin‐1 in ADP‐ or U46619‐treated human umbilical vein endothelial cells. In arterial and pulmonary thrombosis mouse model, MA showed prominent anticoagulant and antithrombotic effects. Our data suggest MA as a candidate molecule for a new class of drugs targeting anti‐FXa and antiplatelet.