Abstract
BackgroundIncreased 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.MethodsInhibitory effect of PTS and its main ginsenosides on agonists-induced platelet aggregation was determined using rabbit or human platelets. Intracellular Ca2+ concentration ([Ca2+]i) mobilization was detected with fura-2/AM probe. MAPKs phosphorylation was determined by Western blotting.ResultsOur 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.ConclusionWe 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.
Highlights
Increased platelet aggregation is implicated in the pathogenesis of ischemic stroke and anti-platelet strategy may contribute to its therapy
Inhibitory effect of Panaxatriol saponin (PTS) on agonist induced rabbit platelet aggregation To determine the effect of PTS on rabbit platelet aggregation, we examined its anti-platelet activity against stimulation of different agonists. washed platelets were pre-incubated with different concentrations of PTS and exposed to collagen, thrombin and adenosine diphosphate (ADP), respectively
Inhibitory effect of the main ginsenosides in PTS on thrombin induced rabbit platelet aggregation As PTS consists of three main ginsenosides (Rg1, Re and R1), we are interested in the effect of these single compounds on rabbit platelet inhibition and asked whether there is a synergistic effect when they are used as a combination
Summary
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. Panaxatriol saponin (PTS) is one of the major components of Panax notoginseng and composed of ginsenoside Rg1 (Rg1), notoginsenoside R1 (R1) and ginsenoside Re (Re) It has been clinically used in China for the treatment of cerebral infarction. In view of the protective effect on ischemic stroke, whether PTS has the anti-platelet activity is drawing our attention. We designed experiments to investigate the effect of PTS on platelet aggregation and explore the underlying mechanisms in the current study
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