title: Antiplatelet, anticoagulant, and profibrinolytic activities of withaferin A.
abstract: Withaferin A (WFA), an active compound from Withania somnifera, is widely researched for its anti-inflammatory, cardioactive and central nervous system effects. However, antiplatelet, anticoagulant, and profibrinolytic properties of WFA have not been studied. In this study, the anticoagulant activities of WFA were measured by monitoring activated partial thromboplastin-time (aPTT), prothrombin time (PT), fibrin polymerization, platelet aggregation, thrombus formation, and the activities of cell-based thrombin and activated factor X (FXa). The effects of WFA 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 (HUVECs). Our data showed that WFA inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation, FeCl3-induced thrombus formation, prolonged aPTT and PT significantly and inhibited the activities and production of thrombin and FXa. WFA prolonged in vivo and ex vivo bleeding time and inhibited TNF-α induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significantly decreased by WFA. Collectively, these results indicate that WFA possesses antithrombotic activities and suggest that the current study could provide bases for the development of new anticoagulant agents.
authors.affiliation: Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 712-715, Republic of Korea.
authors.forename: Sae-Kwang
authors.initials: SK
authors.lastname: Ku
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea. Electronic address: baejs@knu.ac.kr.
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D054358:Withanolides / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D054358:Withanolides; C009684:withaferin A
keywords: Anticoagulant; Fibrinolysis; HUVEC; Withaferin A