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

Abstract

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.

In silico investigation of Panax ginseng lead compounds against COVID-19 associated platelet activation and thromboembolism

“…Previous molecular docking simulation using ginsenoside Rg1 and GPIbα showed that ginsenoside Rg1 forms a stable structure with GPIbα by creating hydrogen bonds with the LEU214, LYS189, CYS211, GLU212, TYR215, ARG17, and THR266 residues of the GPIbα protein [ 23 ]. According to the author, this binding pattern implied that ginseonoside Rg1 inhibits GPIbα activity by occupying the amino acid N-terminal of GPIbα.…”

Herb-paths, a network and statistical model to explore health-beneficial effects of herbs and herbal constituents

“…Quebec Platelet Disorder is a genetic disorder characterized by urokinase-type plasminogen activator (uPA) in platelets, which causes accelerated fibrinolysis and bleeding 43 . Notoginseng has been shown to have anti-platelet activities 12,27 , but an investigation in the treatment of Quebec Platelet Disorder specifically has not been published. However, one Notoginseng constituent (Notoginsenoside R1) has been shown to increase uPA and fibrinolysis 44 , which would aggravate Quebec Platelet Disorder; making Notoginseng /PTS a contraindication for Quebec Platelet Disorder.…”

“…Indeed, two novel CCT diseases showed a significant association to PTS, and four novel CCT diseases showed a significant association to Notoginseng. These included Aortic Aneurysm (a dilation Herb-paths in the aorta which can be caused/aggravated by platelet aggregation 40 ); which might benefit from the anti-platelet treatment provided by Notoginseng/PTS 12,27 .…”

“…To assess associations with CCT disorders, terms describing CCT diseases were first standardized. Terms were manually extracted from 17 scientific articles describing the effects of PTS [11][12][13][14][25][26][27][28] or describing CCT in general [29][30][31][32][33][34][35][36][37] , and transformed into identifiers of the human disease ontology 22 (DOID) (see Figure S1 and Table S2). Ontology tree descendants of the DOID identifiers were subsequently extracted in order to include CCT diseases on all levels of specificity.…”

Effectively Improve Ischemic Stroke’s Strategy: Attenuate Oxidative Stress

“…Ischemic Stroke (IS), also known as cerebral infarction, is one of the most disabling and fatal diseases in cerebrovascular diseases. Due to its high incidence, high disability rate, high mortality rate, and high recurrence rate， IS brings great harm and a heavy economic burden to patients' families and society [1,2] and has an explosive growth trend, posing a great threat to public health [3].…”