title: Decichine enhances hemostasis of activated platelets via AMPA receptors.
abstract: BACKGROUND
  Dencichine, one of the non-protein amino acids present in the roots of Panax notoginseng, has been found to shorten bleeding time of mice and increase the number of platelets. However, the exact underlying mechanisms have not been elucidated yet. This study was aimed to identify the hemostatic effect of dencichine and uncover its mechanisms.
  
  
  METHODS
  Hemostatic effect was assessed by measuring tail bleeding time and coagulation indices of rats. PT, APTT, TT and FIB concentration were measured using a Sysmex CA-1500 plasma coagulation analyzer. Platelet aggregation rate was determined by using a platelet aggregometer. Concentration of cyotosolic calcium was evaluated by Fluo-3 and levels of cyclic adenosine monophosphate (cAMP) and thromboxane A₂ (TXA₂) were measured by ELISA method.
  
  
  CONCLUSIONS
  Dencichine administered orally shortened tail bleeding time, reduced APTT and TT but increased the concentration of FIB in plasma in a dose-dependent manner. When induced with trap, dencichine could elevate the cytoplasmic concentration of calcium, and secretion of TXA₂ as well as the ratio of TXA₂ to PGI₂ from platelets. Meanwhile, it decreased the level of intracellular cAMP. However, CNQX could block the enhanced hemostatic effect of dencichine. These results suggested that dencichine exerted hemostatic function via AMPA receptors on platelets, therefore, facilitated coagulation cascade in a paracrine fashion by control of platelet cytosolic calcium influx, cAMP production and TXA₂ release. Current study may contribute to its clinical use in therapy of hemorrhage.
authors.affiliation: The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Department of Pharmacognosy, China Pharmaceutical University, Nanjing, China.
authors.forename: Ling-Fang
authors.initials: LF
authors.lastname: Huang
authors.affiliation: The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Hai-Lian
authors.initials: HL
authors.lastname: Shi
authors.affiliation: The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Department of Pharmacognosy, China Pharmaceutical University, Nanjing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.affiliation: The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address: xiaojunwu320@126.com.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Wu
authors.affiliation: The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Department of Pharmacognosy, China Pharmaceutical University, Nanjing, China; Shanghai R&D Center for Standardization of Traditional Chinese Medicines, Shanghai, China. Electronic address: wangzht@hotmail.com.
authors.forename: Zheng-Tao
authors.initials: ZT
authors.lastname: Wang
mesh_terms: D000599:Amino Acids, Diamino / Q000494:pharmacology*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006487:Hemostasis / Q000187:drug effects; D008297:Male; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000097:blood*
chemical_list: D000599:Amino Acids, Diamino; D004365:Drugs, Chinese Herbal; D018091:Receptors, AMPA; C100126:oxalyldiaminopropionic acid
keywords: Cyclic adenosine monophosphate; Cytoplasmic calcium; Dencichine; Hemostasis; Platelet aggregation; Thromboxane A(2)