title: Anticoagulant activities of piperlonguminine in vitro and in vivo.
abstract: Piperlonguminine (PL), an important component of Piper longum fruits, is known to exhibit anti-hyperlipidemic, anti-platelet and anti-melanogenic activities. Here, the anticoagulant activities of PL were examined by monitoring activated-partial-thromboplastin-time (aPTT), prothrombin-time (PT), and the activities of thrombin and activated factor X (FXa). The effects of PL 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 HUVECs. The results showed that PL prolonged aPTT and PT significantly and inhibited the activities of thrombin and FXa. PL inhibited the generation of thrombin and FXa in HUVECs. In accordance with these anticoagulant activities, PL prolonged in vivo bleeding time and inhibited TNF-α induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significan- tly decreased by PL. Collectively, our results suggest that PL possesses antithrombotic activities and that the current study could provide bases for the development of new anticoagulant agents.
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Korea baejs@knu.ac.kr.
authors.forename: Wonhwa
authors.initials: W
authors.lastname: Lee
authors.forename: Hayoung
authors.initials: H
authors.lastname: Yoo
authors.forename: Sae-Kwang
authors.initials: SK
authors.lastname: Ku
authors.forename: Jeong Ah
authors.initials: JA
authors.lastname: Kim
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology* / Q000627:therapeutic use*; D002478:Cells, Cultured; D004148:Dioxolanes / Q000494:pharmacology* / Q000627:therapeutic use*; D015951:Factor Xa / Q000378:metabolism; D006470:Hemorrhage / Q000188:drug therapy; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D011517:Prothrombin Time; D013917:Thrombin / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D010881:Piperidones
chemical_list: D000925:Anticoagulants; D004148:Dioxolanes; D015951:Factor Xa; D013917:Thrombin; D010959:Tissue Plasminogen Activator; C498077:piperlongumine; D010881:Piperidones