title: A new anti-fibrinolytic hemostatic compound 8-O-acetyl shanzhiside methylester extracted from Lamiophlomis rotata.
abstract: BACKGROUND
  Fibrinolysis prevents blood clots from growing and becoming problematic. Antifibrinolytics are used as inhibitors of fibrinolysis. Aprotinin was doubted after identification of major side effects, especially on kidney. Lysine analogues has their own defects and whether they are adequate substitutes for aprotinin is still under doubt. Lamiophlomis rotata (Benth.) Kudo. was previous found to have hemostatic activity. But the active compound in L. rotata and its hemostatic mechanism were unknown.
  
  
  OBJECTIVE
  To find the major hemostatic compound in L. rotata and identify its haemostasis mechanism.
  
  
  METHODS
  Traumatic hemorrhage model and coagulant activity assays were monitored in mice and platelets in drug treatment group and control group. Hyperfibrinolysis model was established by intravenous administration of urokinase in mice. Capillary blood clotting time (CBCT), activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen and euglobulin clot lysis time (ECLT) were measured.
  
  
  RESULTS
  The anti-fibrinolytic activity come from 8-O-Acetyl shanzhiside methylester (ASM) one of the highest iridoid glycosides contents in TIG extracted from L. rotata. ASM significantly (P<0.05) shorten CBCT and reduced blood loss volume in vivo, but did not influence mice APTT, PT or TT. In particular, it significantly prolonged ECLT in hyperfibrinolysis mice. It indicated that ASM could inhibit fibrinolysis. ASM was also effective in CBCT, traumatic bleeding volume and ECLT in hyperfibrinolysis mice model.
  
  
  CONCLUSIONS
  ASM was the major hemostatic compound in L. rotata. The haemostasis mechanism of ASM was achieved by anti-fibrinolytic activity. ASM was a new fibrinolysis inhibitor as iridoid glycoside compound.
authors.affiliation: Department of Pharmacy, General Hospital of Lanzhou Command of PLA, Lanzhou, China.
authors.forename: Peng-Cheng
authors.initials: PC
authors.lastname: Fan
authors.affiliation: Department of Pharmacy, General Hospital of Lanzhou Command of PLA, Lanzhou, China.
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Ma
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Lanzhou University, Lanzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Lanzhou University, Lanzhou, China.
authors.forename: Xi-Rui
authors.initials: XR
authors.lastname: He
authors.affiliation: Department of Pharmacy, General Hospital of Lanzhou Command of PLA, Lanzhou, China.
authors.forename: Ai-Jun
authors.initials: AJ
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Lanzhou University, Lanzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Pharmacy, General Hospital of Lanzhou Command of PLA, Lanzhou, China.
authors.forename: Mao-Xing
authors.initials: MX
authors.lastname: Li
authors.affiliation: Department of Pharmacy, General Hospital of Lanzhou Command of PLA, Lanzhou, China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Jing
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Lanzhou University, Lanzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Pharmacy, General Hospital of Lanzhou Command of PLA, Lanzhou, China. Electronic address: majunbox@sina.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, General Hospital of Lanzhou Command of PLA, Lanzhou, China; Department of Pharmaceutics, School of Pharmacy, Lanzhou University, Lanzhou, China. Electronic address: pharmapaper@hotmail.com.
authors.forename: Zheng-Ping
authors.initials: ZP
authors.lastname: Jia
mesh_terms: D000818:Animals; D000933:Antifibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D005342:Fibrinolysis / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D006470:Hemorrhage / Q000188:drug therapy*; D019686:Lamiaceae; D008297:Male; D008807:Mice, Inbred BALB C; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D011714:Pyrans / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000933:Antifibrinolytic Agents; D005960:Glucosides; D011714:Pyrans; C099473:8-O-acetyl shanzhiside methyl ester
keywords: Antifibrinolytics; Bleeding volume; Hemostatics; Hyperfibrinolysis; Iridoid glycosides