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

2020 ◽  
Author(s):  
Zhiyi Xu ◽  
Yang Xu ◽  
Xiaofang Xie ◽  
Yin Tian ◽  
Junhui Sui ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Platelet Aggregation ◽  
Platelet Adhesion ◽  
Ischemia Reperfusion ◽  
Panax Notoginseng ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Stroke Therapy ◽  
Related Factors ◽  
Model Animal

Abstract 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.

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

2021 ◽  
Author(s):  
Zhiyi Xu ◽  
Yang Xu ◽  
Xiaofang Xie ◽  
Yin Tian ◽  
Junhui Sui ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Platelet Aggregation ◽  
Platelet Adhesion ◽  
Ischemia Reperfusion ◽  
Panax Notoginseng ◽  
Molecular Evidence ◽  
Therapeutic Effects ◽  
Stroke Therapy ◽  
Related Factors ◽  
Model Animal

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.

scholarly journals Anti-platelet aggregation of Panax notoginseng triol saponins by regulating GP1BA for ischemic stroke therapy

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Zhi-yi Xu ◽  
Yang Xu ◽  
Xiao-fang Xie ◽  
Yin Tian ◽  
Jun-hui Sui ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Platelet Aggregation ◽  
Platelet Adhesion ◽  
Ischemia Reperfusion ◽  
Panax Notoginseng ◽  
Molecular Evidence ◽  
Therapeutic Effects ◽  
Stroke Therapy ◽  
Related Factors ◽  
Model Animal

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.

scholarly journals Anti-Platelet Aggregation of Panax Notoginseng Triol Saponins by regulating GP1BA for Ischemic Stroke Therapy

2020 ◽  
Author(s):  
Zhiyi Xu ◽  
Yang Xu ◽  
Xiaofang Xie ◽  
Yin Tian ◽  
Junhui Sui ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Platelet Aggregation ◽  
Platelet Adhesion ◽  
Ischemia Reperfusion ◽  
Panax Notoginseng ◽  
Artery Occlusion ◽  
Receptor Expression ◽  
Stroke Therapy ◽  
Related Factors ◽  
Platelet Receptor

Abstract 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.

scholarly journals Novel Therapeutic Effects of Leonurine On Ischemic Stroke: New Mechanisms of BBB Integrity

2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Qiu-Yan Zhang ◽  
Zhi-Jun Wang ◽  
De-Miao Sun ◽  
Ying Wang ◽  
Peng Xu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Tight Junction ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Brain Diseases ◽  
Therapeutic Effects ◽  
Protective Effects

Stroke is a leading cause of morbidity and mortality globally. Leonurine (also named SCM-198), a compound extracted fromHerba leonuri, was effective on the prevention of various cardiovascular and brain diseases. The purpose of this study was to explore the possible therapeutic potential of SCM-198 against ischemia reperfusion injury and underlying mechanisms. In the in vivo transient middle cerebral artery occlusion (tMCAO) rat model, we found that treatment with SCM-198 could decrease infarct volume and improve neurological deficit by protecting against blood-brain barrier (BBB) breakdown. In the in vitro model of cell oxygen-glucose deprivation and reoxygenation (OGD/R), consistent results were obtained with decreased reactive oxygen species (ROS) production and maintained the BBB integrity. Further study demonstrated that SCM-198 increased the expression of histone deacetylase- (HDAC-) 4 which could inhibit NADPH oxidase- (NOX-) 4 and matrix metalloproteinase- (MMP-) 9 expression, resulting in the elevation of tight junction proteins, including claudin-5, occludin, and zonula occluden- (ZO-) 1. These results indicated SCM-198 protected BBB integrity by regulating the HDAC4/NOX4/MMP-9 tight junction pathway. Our findings provided novel insights into the protective effects and mechanisms of SCM-198 on ischemic stroke, indicating SCM-198 as a new class of potential drug against acute onset of ischemic stroke.

scholarly journals Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3β axis

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Jian-Ping Zhang ◽  
Wei-Jing Zhang ◽  
Miao Yang ◽  
Hua Fang
Keyword(s):  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Loss Of Function

Abstract Background Propofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β). Methods C57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured. Results Our experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression. Conclusion Overall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.

scholarly journals Protective effects of ginsenoside Rg1 on intestinal ischemia/reperfusion injury-induced oxidative stress and apoptosis via activation of the Wnt/β-catenin pathway

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Guo Zu ◽  
Jing Guo ◽  
Ningwei Che ◽  
Tingting Zhou ◽  
Xiangwen Zhang
Keyword(s):  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Ginsenoside Rg1 ◽  
Intestinal Ischemia Reperfusion

Abstract Ginsenoside Rg1 (Rg1) is one of the major bioactive ingredients in Panax ginseng, and it attenuates inflammation and apoptosis. The aims of our study were to explore the potential of Rg1 for the treatment of intestinal I/R injury and to determine whether the protective effects of Rg1 were exerted through the Wnt/β-catenin signaling pathway. In this study, Rg1 treatment ameliorated inflammatory factors, ROS and apoptosis that were induced by intestinal I/R injury. Cell viability was increased and cell apoptosis was decreased with Rg1 pretreatment following hypoxia/reoxygenation (H/R) in the in vitro study. Rg1 activated the Wnt/β-catenin signaling pathway in both the in vivo and in vitro models, and in the in vitro study, the activation was blocked by DKK1. Our study provides evidence that pretreatment with Rg1 significantly reduces ROS and apoptosis induced by intestinal I/R injury via activation of the Wnt/β-catenin pathway. Taken together, our results suggest that Rg1 could exert its therapeutic effects on intestinal I/R injury through the Wnt/β-catenin signaling pathway and provide a novel treatment modality for intestinal I/R injury.

Therapeutic effects of different treatment periods against ischemic stroke and toxicology study of Angong Niuhuang Pill in rats

2020 ◽  
Author(s):  
Jianzhao Chen ◽  
Yushuang Chai ◽  
Yuanfeng He ◽  
Jisheng Huang ◽  
Ting Wan ◽  
...  
Keyword(s):  
Body Weight ◽  
Ischemic Stroke ◽  
Protective Effect ◽  
Toxic Effect ◽  
Treatment Period ◽  
Ischemia Reperfusion ◽  
Neurological Function ◽  
The Body ◽  
Therapeutic Effects ◽  
Toxicology Study

Abstract Background : Angong Niuhuang Pill (ANP) is one of the most famous drugs to treat stroke in China, but there is no definite treatment period in drug instruction. In this study, we used middle cerebral artery occlusion (MCAO) model to evaluate its therapeutic effects of different treatment periods and studied its toxic effect in rats. Methods : Protective effect of ANP was observed in the cerebral ischemia-reperfusion model in rats; ANP (270 mg/kg) three different treatment period included 1 day, 4 days and 7 days. The observation period was 30 days. Therapeutic effect was evaluated by detecting neurological function, cerebral infraction volume, brain histology and cytokines. Three dose including 550, 1640, 4910 mg/kg were studied in toxicology study. The administration period was 30 days. Toxic effect was evaluated by detecting appearance, behavior, excrement character, food-intake, body weight, hematological parameters and biomarkers such as TBA, GSTα, Cystatin C, clusterin, GSH, S-100B and MBP. Results : Seven days treatment period of ANP had better effect than 1 day and 4 days treatment periods in rat MCAO model from neurological function scores, the volume of cerebral infarction, brain histology and the serum content of IL-1β, TNF-α and NO; the brain content of IL-1β and NO. The results of 30 days multiple dose toxicology study showed no animal death in all groups; in ANP 4910 mg/kg group, the kidney and liver coefficient increased about 10%, the body weight grew more slowly, the TBA increased slightly. There was no abnormal change in histology. These all recovered after drug withdraw for 8 weeks. Conclusion: Seven days treatment period of ANP had more protective effect than 1 day and 4 days treatment periods in ischemic stroke rat. No observed adverse effect level (NOAEL) of ANP was 1640 mg/kg; the safety margin of ANP was 270-1640 mg/kg. These data provided reference to modify drug instruction.

scholarly journals STUDY ON THE SYNTHESIS OF PUERARIN DERIVATIVES AND THEIR ANTI-VASCULAR DEMENTIA ACTIVITY

2016 ◽  
Vol 8 (2) ◽  
pp. 11
Author(s):  
Pei Jiang
Keyword(s):  
Vascular Dementia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cyclooxygenase 2 ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
H Nmr ◽  
Cox 2 ◽  
Oxide Synthase

<p class="lead">In this study, puerarin derivatives were designed by adding an active acetonitrile group that inhibits cyclooxygenase-2 (COX-2) in order to enhance the anti-vascular dementia drug activity. The acetonitrile group was linked to puerarin at the 7/4 'positions by a phenolic hydroxyl to give 7-mono-and 7, 4' di-substituted derivatives of puerarin. These structures were confirmed by <sup>1</sup>H NMR spectroscopy and MS spectroscopy. We compared the affinity of puerarin derivatives and puerarin for cyclooxygenase-2 (COX-2) using molecular docking. In addition, the anti-vascular dementia activity of the developed puerarin derivatives was studied by water maze, novel object recognition, and the determination of inducible nitric oxide synthase (iNOS) enzyme activity at the cerebral cortex of mice. Experimental results showed that the puerarin derivatives have a good affinity for COX-2 with therapeutic effects against vascular dementia. The results of this study suggest that the protective effects of the puerarin derivatives against vascular dementia may be related to suppression of inflammation associated with ischemia-reperfusion injury through inhibition of COX-2.</p>

scholarly journals Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Lei Liu ◽  
Qiongling Zhang ◽  
Shunli Xiao ◽  
Zhengxiao Sun ◽  
Shilan Ding ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Adhesion ◽  
Panax Notoginseng ◽  
Underlying Mechanism ◽  
Cerebrovascular Diseases ◽  
Signal Pathway ◽  
Therapeutic Action ◽  
Aggregation Assay ◽  
Platelet Aggregation Assay ◽  
Calpain 2

XueShuanTong (XST) comprising therapeutically active ginsenosides, a lyophilized extract of Panax notoginseng roots, is extensively used in traditional Chinese medicine to treat ischemic heart and cerebrovascular diseases. Our recent study shows that treatment with XST inhibits shear-induced thrombosis formation but the underlying mechanism remained unclear. This study aimed to investigate the hypothesis that XST inhibited shear-induced platelet aggregation via targeting the mechanosensitive Ca2+-permeable Piezo1 channel by performing platelet aggregation assay, Ca2+ imaging and Western blotting analysis. Exposure to shear at physiologically (1,000–2000 s−1) and pathologically related rates (4,000–6,000 s−1) induced platelet aggregation that was inhibited by treatment with GsMTx-4. Exposure to shear evoked robust Ca2+ responses in platelets that were inhibited by treatment with GsMTx-4 and conversely enhanced by treatment with Yoda1. Treatment with XST at a clinically relevant concentration (0.15 g L−1) potently inhibited shear-induced Ca2+ responses and platelet aggregation, without altering vWF-mediated platelet adhesion and rolling. Exposure to shear, while resulting in no effect on the calpain-2 expression in platelets, induced calpain-2-mediated cleavage of talin1 protein, which is known to be critical for platelet activation. Shear-induced activation of calpain-2 and cleavage of talin1 were attenuated by treatment with XST. Taken together, our results suggest that XST inhibits shear-induced platelet aggregation via targeting the Piezo1 channel to prevent Piezo1-mediated Ca2+ signaling and downstream calpain-2 and talin1 signal pathway, thus providing novel insights into the mechanism of the therapeutic action of XST on platelet aggregation and thrombosis formation.

scholarly journals lncRNA AK054386 Functions as a ceRNA to Sequester miR-199 and Induce Sustained Endoplasmic Reticulum Stress in Hepatic Reperfusion Injury

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Binghua Dai ◽  
Liang Qiao ◽  
Mingke Zhang ◽  
Lipeng Cheng ◽  
Ling Zhang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Liver Trauma ◽  
Protective Effects ◽  
Related Factors ◽  
Hepatic Ischemia ◽  
Cellular Models

Hepatic ischemia-reperfusion injury (IRI) is a very complex pathological process that is often associated with liver trauma and surgery, especially liver transplantation surgery. Although endoplasmic reticulum stress (ERS) plays a role in this process, the posttranscriptional regulators and the underlying mechanisms are still unclear. Here, we report that the lncRNA AK054386 was increased in hepatic IRI models. Furthermore, AK054386 can act as a “competing endogenous RNA (ceRNA)” and regulate ERS-related factors by binding and sequestering miR-199, which was shown to inhibit ERS in our previous report. Increased expression of AK054386, which might be mediated by activated NF-κB, resulted in sustained ERS and increased cell apoptosis and death in hepatic IRI mouse and cellular models. In contrast, AK054386 inhibition had protective effects on these models. Our data indicate that AK054386 and miR-199 are critical players in hepatic IRI, and we broadened the scope regarding ceRNA mechanisms. We hope that our results will improve the understanding of hepatic IRI and may provide potential therapeutic targets.

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