Zhi-Yi Xu1,2, Yang Xu1, Xiao-Fang Xie3, Yin Tian3, Jun-Hui Sui1, Yong Sun1, Da-Sheng Lin3,2, Xing Gao2, Cheng Peng4, Yu-Jiang Fan5. 1. National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu, 610064, Sichuan, China. 2. Chengdu Huasun Technology Group Inc., Ltd, Shuxin Avenue No.1168, Western Hi-tech Zone, Chengdu, 611731, Sichuan, China. 3. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Liutai Avenue NO. 1166, Wenjiang District, Chengdu, 611137, Sichuan, China. 4. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Liutai Avenue NO. 1166, Wenjiang District, Chengdu, 611137, Sichuan, China. pengchengchengdu@126.com. 5. National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu, 610064, Sichuan, China. fan_yujiang@scu.edu.cn.
Abstract
BACKGROUND: Panax notoginseng triol saponins (PTS) has been used clinically for ischemic stroke therapy (IST) in China for more than 17 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 17 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.
Authors: Simon F De Meyer; Tommy Andersson; Blaise Baxter; Martin Bendszus; Patrick Brouwer; Waleed Brinjikji; Bruce Cv Campbell; Vincent Costalat; Antoni Dávalos; Andrew Demchuk; Diederik Dippel; Jens Fiehler; Urs Fischer; Michael Gilvarry; Matthew J Gounis; Jan Gralla; Olav Jansen; Tudor Jovin; David Kallmes; Pooja Khatri; Kennedy R Lees; Elena López-Cancio; Charles Majoie; Henk Marquering; Ana Paula Narata; Raul Nogueira; Peter Ringleb; Adnan Siddiqui; István Szikora; David Vale; Rüdiger von Kummer; Albert J Yoo; Werner Hacke; David S Liebeskind Journal: Int J Stroke Date: 2017-05-23 Impact factor: 5.266