Anti-platelet activity of panaxatriol saponins is mediated by suppression of intracellular calcium mobilization and ERK2/p38 activation.
BACKGROUND
Increased platelet aggregation is implicated in the pathogenesis of ischemic stroke and anti-platelet strategy may contribute to its therapy. Panaxatriol saponin (PTS), the main components extracted from Panax notoginseng, has been shown to be efficacious in the prevention and treatment of ischemic stroke in China. The aim of this study is to determine the anti-platelet activity and explore the underlying mechanisms.


METHODS
Inhibitory effect of PTS and its main ginsenosides on agonists-induced platelet aggregation was determined using rabbit or human platelets. Intracellular Ca(2+) concentration ([Ca(2+)]i) mobilization was detected with fura-2/AM probe. MAPKs phosphorylation was determined by Western blotting.


RESULTS
Our results showed PTS inhibited the rabbit platelet aggregation induced by various agonists (collagen, thrombin and ADP). The three main ginsenosides (Rg1, Re and R1) existing in PTS also showed anti-platelet activity, while their combination exhibited no synergistic effect on rabbit platelet aggregation. Further study demonstrated that PTS and its main ginsenosides also exhibited inhibitory effect on human platelet aggregation. Mechanism study demonstrated that pre-treatment with PTS inhibited the agonists-induced intracellular calcium mobilization. Moreover, PTS significantly suppressed the activation of both ERK2 and p38 by the agonists via reducing the phosphorylation of ERK2 and p38.


CONCLUSIONS
We proved that PTS is effective in anti-platelet aggregation, which may, at least in part, be related to the suppression of intracellular calcium mobilization and ERK2/p38 activation. This study may provide one reasonable explanation for the efficacy of PTS on the prevention and treatment of ischemic stroke.
College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing, 400716, China.
Hongyi
H
Qi
Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, Sichuan, China.
Yongliang
Y
Huang
College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing, 400716, China.
Yi
Y
Yang
College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing, 400716, China.
Guojun
G
Dou
Huasun Group Co., Ltd., Chengdu, 610072, Sichuan, China.
Fang
F
Wan
Huasun Group Co., Ltd., Chengdu, 610072, Sichuan, China.
Wenwu
W
Zhang
Huasun Group Co., Ltd., Chengdu, 610072, Sichuan, China.
Huarong
H
Yang
Huasun Group Co., Ltd., Chengdu, 610072, Sichuan, China.
Li
L
Wang
College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, China.
Chunjie
C
Wu
College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing, 400716, China. lilyli029@126.com.
Li
L
Li
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D053723:Panax notoginseng / Q000737:chemistry*; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D020521:Stroke / Q000517:prevention & control; D013917:Thrombin / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D036145:Ginsenosides; D010975:Platelet Aggregation Inhibitors; C004563:panaxatriol; D019950:Mitogen-Activated Protein Kinase 1; D048051:p38 Mitogen-Activated Protein Kinases; D013917:Thrombin; D002118:Calcium
Intracellular calcium mobilization; Panaxatriol saponin; Platelet aggregation; p-ERK2; p-p38