Background: Panax notoginseng triol saponins (PTS) has been used clinically for ischemic stroke therapy (IST) in China for more than seventeen years due to its anti-platelet aggregation and neuro-protective effects, but its mechanism of action is not fully understand. In this study, anti-platelet aggregation-related protein analysis and computer simulations of drug-protein binding interactions were performed to explore the mechanism of the effects of PTS against ischemic stroke in an ischemia reperfusion model. Methods: Three oral doses of PTS were administered in a model of middle cerebral artery occlusion (MCAO) in rats. Panax notoginseng total saponins (PNS) and a combination of PTS and aspirin were chosen for comparison. To evaluate therapeutic effects and explore possible mechanisms of anti-platelet aggregation, we measured cerebral infarct size and water content in brain tissue, histomorphological changes, expression of related factors (such as arachidonic acid metabolites) and platelet receptors in serum, as well as the binding affinity of PTS for platelet adhesion receptors. Results: Compared with PNS, PTS showed a stronger and more potent anti-platelet aggregation effect in MCAO model rats. The combination of PTS and aspirin could reduce adverse gastrointestinal effects by regulating the TXA2/PGI2 ratio. We demonstrated for the first time that PTS was able to regulate Glycoprotein Ib-α (GP1BA) in a model animal. The binding of ginsenoside Rg1 and GP1BA could form a stable structure. Moreover, PTS could reduce von Willebrand factor (VWF)-mediated platelet adhesion to damaged vascular endothelium, and thus enhance the probability of anti-platelet aggregation and anti-thrombosis under pathological conditions.Conclusions: Our results showed that GP1BA was closely related to the anti-platelet aggregation action of PTS, which provided new scientific and molecular evidence for its clinical application.
Background: Panax notoginseng triol saponins (PTS) has been used clinically for ischemic stroke therapy (IST) in China for more than sixteen years due to its anti-platelet aggregation and neuro-protective effects, but its mechanism of action is still unclear. In this study, anti-platelet aggregation-related protein analysis and computer simulations of drug-protein binding interactions were performed to explore the mechanism of the effects of PTS against ischemic stroke in an ischemia reperfusion model. Methods: Three oral doses of PTS were administered in a model of middle cerebral artery occlusion (MCAO) in rats. Panax notoginseng total saponins (PNS) and a combination of PTS and aspirin were chosen for comparison. To evaluate therapeutic effects and explore possible mechanisms of anti-platelet aggregation, we measured cerebral infarct size and water content in brain tissue, histomorphological changes, expression of related factors (such as arachidonic acid metabolites) and platelet receptors in serum, as well as the binding affinity of PTS for platelet adhesion receptors. Results: Compared with PNS, PTS showed a stronger and more extensive anti-platelet aggregation effect in MCAO model rats. The combination of PTS and aspirin could reduce adverse gastrointestinal effects by regulating the TXA2/PGI2 ratio. PTS was found to regulate Glycoprotein Ib-α (GP1BA) in a model animal for the first time, and they had a relatively stable binding ability, especially ginsenoside Rg1 and GP1BA, which could form a stable structure. However, PTS could reduce von Willebrand factor (VWF)-mediated platelet adhesion to damaged vascular endothelium, and thus enhance the probability of anti-platelet aggregation and anti-thrombosis under pathological conditions.Conclusions: Our results showed that GP1BA was closely related to the anti-platelet aggregation action of PTS, which provided new scientific evidence for its clinical application.
Background: Panax notoginseng triol saponins (PTS) has been used clinically for ischemic stroke therapy (IST) by potential anti-platelet aggregation and neuro-protective in China for more than sixteen years, but its mechanisms are still unclear. In this study, anti-platelet aggregation related protein analysis and computer simulations of drug-protein binding interactions were performed for exploring mechanism of PTS against ischemic stroke by ischemia reperfusion model. Methods: Three doses of PTS were administered orally in middle cerebral artery occlusion (MCAO) model rats; Panax notoginseng total saponins (PNS) and the combination of PTS and aspirin were chosen as comparison. The cerebral infarct size and water content in brain tissue, histomorphological observation, related factors and platelet receptor expression in serum, as well as binding affinity of PTS and platelet adhesion receptor were detected to evaluate therapeutic effect and explore possible mechanisms of anti-platelet aggregation. Results: Compared with PNS, PTS showed stronger and more extensive anti-platelet aggregation effect on MCAO model rats. The combination of PTS and aspirin might reduce the gastrointestinal adverse reactions by regulating TXA2/PGI2 ratio. However, PTS could reduce the chance of VWF-mediated platelet adhesion to damaged vascular endothelium, and thus enhance the probability of anti-platelet aggregation and anti-thrombosis under pathological conditions.Conclusion: Our results showed that GP1BA was closely related with anti-platelet aggregation action of PTS, which provided new scientific evidences for its clinical application.
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