Anti-Platelet Aggregation of Panax Notoginseng Triol Saponins by Regulating GP1BA for Ischemic Stroke Therapy [post]

Zhiyi Xu, Yang Xu, Xiaofang Xie, Yin Tian, Junhui Sui, Yong Sun, Dasheng Lin, Xing Gao, Cheng Peng, Yujiang Fan
2020 unpublished
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
more » ... 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.
doi:10.21203/rs.3.rs-55926/v2 fatcat:7q7mdefdmbgnfboc3obzieflby