title: Ginsenoside Rg1 inhibits platelet activation and arterial thrombosis.
abstract: BACKGROUND
  Derived from the root of Panax ginseng C.A.Mey, Panax notoginsenosides (PNS) is a widely used herbal medicine to treat atherothrombotic diseases in Asian medicine. Ginsenoside Rg1 is one of the main compounds responsible for the pharmaceutical actions of PNS. As platelets play pivotal roles in atherothrombogenesis, we therefore studied the effect of Rg1 on platelet activation and its underlying mechanisms.
  
  
  METHODS
  Human platelets are obtained from healthy subjects. Platelet activation and the inhibition of Rg1 were assessed by Born aggregometer, flow cytmetry, flow chamber and western blot. The in vivo thrombosis model was induced by 10% FeCl3 on mesenteric arterioles of wild type B57/b6 mice.
  
  
  RESULTS
  Rg1 significantly inhibited platelet aggregation induced by thrombin, ADP, collagen and U46619, e.g., aggregation rate stimulated by 0.1UmL(-1) thrombin was decreased 46% by Rg1. Rg1 also reduced thrombin (0.1UmL(-1))-enhanced fibrinogen binding and P-selectin expression of single platelet by 81% and 66%, respectively. Rg1 affected αIIbβ3-mediated outside-in signaling as demonstrated by diminished platelet spreading on immobilized fibrinogen. Rg1 also decreased the rate of clot retraction in platelet rich plasma. Furthermore, Rg1 decreased platelet adhesion on collagen surface under a shear rate correlated to the arterial flow (1000s(-1)) by approximately 70%. Western blot showed that Rg1 potently inhibited ERK phosphrylation. The in vitro findings were further evaluated in the mouse model of in vivo arterial thrombosis, and Rg1 was found to prolong the mesenteric arterial occlusion time (34.9±4.1min without and 64.3±4.9min with Rg1; p<0.01).
  
  
  CONCLUSIONS
  Rg1 inhibits platelet activation via the inhibition of ERK pathway, and attenuates arterial thrombus formation in vivo.
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Dongjiao
authors.initials: D
authors.lastname: Luo
authors.affiliation: Department of Cardiology, Lishui Central Hospital, Lishui, China.
authors.forename: Chunlai
authors.initials: C
authors.lastname: Zeng
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yue
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Xiaosheng
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China. Electronic address: huhu@zju.edu.cn.
authors.forename: Hu
authors.initials: H
authors.lastname: Hu
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D015398:Signal Transduction; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy; D055815:Young Adult
chemical_list: D036145:Ginsenosides; D005340:Fibrinogen; C035054:ginsenoside Rg1
keywords: Arterial thrombosis; BSA; CDDPs; COX; Compound Danshen Dripping Pills; ERK; Ginsenoside Rg1; MAPKs; PARs; PBS; PKC; PLCβ; PNS; Platelet; Rg1; SAA; SDS polyacrylamide gel electrophoresis; SDS-PAGE; TXA(2); Thrombin; bovine serum albumin; cyclooxygenase; ginsenoside Rg1; mitogen-activated protein kinases; panax notoginsenosides; phosphate-buffered saline; phospholipase C β; protein kinase C; proteinase-activated receptors; salvianolic acid A; thromboxane A(2)