Novel factor Xa inhibitor, maslinic acid, with antiplatelet aggregation activity.
Kyung-Min KimJaehong KimMoon-Chang BaekJong Sup BaePublished in: Journal of cellular physiology (2020)
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 A2 (TXA2 ) 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.
Keyphrases
- atrial fibrillation
- nitric oxide
- endothelial cells
- mouse model
- venous thromboembolism
- pulmonary embolism
- high glucose
- pulmonary hypertension
- poor prognosis
- protein kinase
- hydrogen peroxide
- electronic health record
- body mass index
- signaling pathway
- drug delivery
- cancer therapy
- oxidative stress
- machine learning
- drug induced
- artificial intelligence