title: Antithrombotic activities of pellitorine in vitro and in vivo.
abstract: Pellitorine (PLT), an active amide compound, is well known to possess insecticidal, antibacterial and anticancer properties. However, the anti-coagulant functions of PLT are not studied yet. Here, the anticoagulant activities of PLT were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of cell-based thrombin and activated factor X (FXa). Furthermore, the effects of PLT on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were tested in tumor necrosis factor (TNF)-α activated human umbilical vein endothelial cells (HUVECs). Treatment with PLT resulted in prolonged aPTT and PT and inhibition of the activities of thrombin and FXa, and PLT inhibited production of thrombin and FXa in HUVECs. And PLT inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In accordance with these anticoagulant activities, PLT elicited anticoagulant effects in mouse. In addition, treatment with PLT resulted in the inhibition of TNF-α-induced production of PAI-1 and in the significant reduction of the PAI-1 to t-PA ratio. Collectively, PLT possesses antithrombotic activities and offers bases for development of a novel anticoagulant.
authors: Department of Anatomy and Histology, College of Oriental Medicine, Daegu Haany University, Gyeongsan 712-715, Republic of Korea.
authors: Sae-Kwang
authors: SK
authors: Ku
authors: Department of Cosmetic Science and Technology, Seowon University, Cheongju 361-742, Republic of Korea.
authors: In-Chul
authors: IC
authors: Lee
authors: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701 Republic of Korea.
authors: Jeong Ah
authors: JA
authors: Kim
authors: 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: Jong-Sup
authors: JS
authors: Bae
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D030023:Asarum / Q000737:chemistry*; D015951:Factor Xa / Q000096:biosynthesis; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005337:Fibrin / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D010314:Partial Thromboplastin Time; D010936:Plant Extracts / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D011517:Prothrombin Time; D013917:Thrombin / Q000096:biosynthesis; D013927:Thrombosis / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D005231:Fatty Acids, Unsaturated; D010936:Plant Extracts; D017395:Plasminogen Activator Inhibitor 1; D010975:Platelet Aggregation Inhibitors; D053284:Polyunsaturated Alkamides; D014409:Tumor Necrosis Factor-alpha; C008778:pellitorine; D005337:Fibrin; D013917:Thrombin; D015951:Factor Xa; D010959:Tissue Plasminogen Activator
keywords: Coagulation cascade; Endothelium; Fibrinolysis; Pellitorine