Antiplatelet, anticoagulant, and profibrinolytic activities of cudratricusxanthone A.
Cudratricusxanthone A (CTXA), a natural bioactive compound extracted from the roots of Cudrania tricuspidata Bureau, is known to possess hepatoprotective, antiproliferative and anti-inflammatory activities. However, antiplatelet, anticoagulant, and profibrinolytic properties have not been studied. The anticoagulant activities of CTXA were measured by monitoring activated partial thromboplastin-time (aPTT), prothrombin time (PT), and the activities of cell-based thrombin and activated factor X (FXa). The effects of CTXA on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were also tested in tumor necrosis factor-α (TNF-α) activated human umbilical vein endothelial cells. Our data showed that CTXA inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation, prolonged aPTT and PT significantly and inhibited the activities and production of thrombin and FXa. CTXA prolonged in vivo bleeding time and inhibited TNF-α induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significantly decreased by CTXA. Collectively, these results indicate that CTXA possesses antithrombotic activities and suggest that the current study could provide bases for the development of new anticoagulant agents.
Hayoung
H
Yoo
Sae-Kwang
SK
Ku
Wonhwa
W
Lee
Soyoung
S
Kwak
Young-Doo
YD
Baek
Byung-Woon
BW
Min
Gil-Saeng
GS
Jeong
Jong-Sup
JS
Bae
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015951:Factor Xa / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D029586:Moraceae / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism; D044004:Xanthones / Q000008:administration & dosage / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; D010975:Platelet Aggregation Inhibitors; D044004:Xanthones; C533013:cudratricusxanthone A; D013917:Thrombin; D015951:Factor Xa