Platelet Protease Activated Receptor 1 Is Involved in the Hemostatic Effect of 20(S)-Protopanaxadiol by Regulating Calcium Signaling

Zhang, He; Pan, Daian; Wu, Xueqing; Su, Wenjie; Tang, Xiaolei; Zhao, Deyu; Sun, Liwei; Song, Bailin; Bai, Xueyuan; Li, Xiangyan

doi:10.3389/fphar.2020.549150

Cited by 6 publications

(11 citation statements)

References 61 publications

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“…Platelet function reagents for thrombin (Chrono-Log Corporation, Pennsylvania, USA) and Fluo-3 AM calcium indicators (Beyotime Biotechnology, Shanghai, China) were used in this study. measured in two mice models [4,28]. 40 male Kunming mice were randomly divided into five groups, including normal saline (NS), hemocoagulase (HC), and PD groups with different doses of 2, 4, and 8 mg/kg PD.…”

Section: Methodsmentioning

confidence: 99%

“…Blood Routine Test. Blood samples from 40 Wister male rats (200:0 ± 10:0 g) of five groups, including NS, HC, and PD groups (2, 4, and 8 mg/kg) were withdrawn from the abdominal aorta and placed in an anticoagulant tube with EDTA to perform routine blood analysis by using the XT-2000i automated hematology analyzer (Sysmex Corporation, Japan), as described previously [4].…”

Section: Methodsmentioning

confidence: 99%

“…Compendium of materia medica recorded that Panax notoginseng could stanch bleeding, disperse blood stasis, relieve pain, and treat most blood diseases. Yu Qiu Yao Jie recorded that Panax notoginseng had the effects of heying hemostasis, dredging blood vessels, removing blood stasis, and gathering new blood [ 4 ]. In Chinese Pharmacopeia, Panax notoginseng possesses the function of promoting blood circulation and removing blood stasis, hemostasis, detumescence, and pain relief.…”

Section: Introductionmentioning

confidence: 99%

“…It cures various kinds of bleeding, pain, and swelling. At present, dencichine [ 5 ], notoginsenoside Ft1 [ 6 ], and PPD [ 4 ] reduced the bleeding time of model mice and induced platelet aggregation that showed the hemostatic effect. Despite ongoing endeavors, we think still some hemostatic ingredients are undiscovered.…”

Section: Introductionmentioning

confidence: 99%

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Hemostatic Effect of 20(S)-Panaxadiol by Induced Platelet Aggregation Depending on Calcium Signaling Pathway

Zhang

Tang

et al. 2022

BioMed Research International

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Panax notoginseng (Burk.) F.H. Chen is the most traditional hemostatic herb in China. Our previous research found that 20(S)-protopanaxadiol showed the hemostatic effect. And 20(S)-panaxadiol (PD) has a similar structure to 20(S)-protopanaxadiol with a dammarane skeleton. So, this article mainly studies the hemostatic effect of PD. The mouse tail amputation and liver scratch models were used to detect the hemostatic effect of PD. Blood routine and plasma coagulation parameters were measured by using a blood analyzer. The platelet aggregometer analyzed the platelet aggregation rate and adenosine triphosphate (ATP) concentration. Moreover, the intracellular calcium concentration ([Ca2+]i), P-selectin (CD62P), PAC-1 (GP IIb/IIIa receptor marker), and cyclic adenosine monophosphate (cAMP) of platelets were also detected. The results showed that PD obviously shortened the bleeding time of the model mouse, affected the RBC and PLT parameters of rats, reduced APTT and TT, elevated FIB concentration, and promoted human/rat-washed platelet aggregation in vitro. PD promoted the release of ATP and [Ca2+]i and slightly increased the expression of CD62P and PAC-1 of platelets without 1 mM Ca2+. After adding 1 mM Ca2+, PD obviously increased ATP releasing and CD62P and GP IIb/IIIa expression rate and decreased the cAMP level of platelets. These parameter changes of PD-caused platelet were inhibited by vorapaxar. Besides, PD increased the phosphorylation of phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase 3β (PI3K/Akt/GSK3β) of human platelets. PD is an important hemostatic ingredient in Panax notoginseng, which induced platelet aggregation by affecting the calcium signaling and activating the PI3K/Akt/GSK3β signaling pathway.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hemostatic Effect of 20(S)-Panaxadiol by Induced Platelet Aggregation Depending on Calcium Signaling Pathway

Zhang

Tang

et al. 2022

BioMed Research International

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“…But, until now, few studies have shown that 20(S)-PD affects the blood system. We have found in previous study that PPD can promote the hemostatic of model bleeding rats and induce platelet aggregation by regulating calcium signaling [19]. Gao et al reported that PPD increased ADP-induced platelet aggregation [10].…”

Section: Introductionmentioning

confidence: 91%

20(S)-Panaxadiol Enhances Hemostatic Effect on Activated Platelet by Affecting Calcium Signaling

Zhang¹,

Su²,

Yang³

et al. 2021

Preprint

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Background: Panax notoginseng (Burk.) F.H. Chen has long been used to stop bleeding for hundreds of years in China. At present, only dencichine and notoginsenoside Ft1 showed the hemostatic effect. Other ingredients from Panax notoginseng need to be further investigated. This study evaluates the hemostatic effect of 20(S)-panaxadiol (PD) and reveals its mechanism. Methods: We performed an in vivo study to measure PD on the hemostatic effect of mouse tail amputation and liver scratch models, and routine blood. Plasma coagulation parameters were measured using a blood analyzer. Platelet aggregation rate and adenosine triphosphate (ATP) release were analyzed by platelet aggregometer. Subsequently, degranulation marker P-selectin (CD62P), PAC-1 (activated GP IIb/IIIa receptor marker), the concentrations of cytosolic Ca2+ ([Ca2+]i) and cyclic adenosine monophosphate (cAMP) were also assessed. Results: PD shorted bleeding time on the mouse tail amputation and liver scratch models and mainly increased blood platelet count in the rats after subcutaneous injection of 4 h. Meanwhile, PD decreased APTT, increased FIB content, and directly induced platelet aggregation. In the absence of Ca2+, PD promoted the increase of [Ca2+]i and ATP, slightly increased CD62P expression and PAC-1 binding of platelets. After the addition of Ca2+, PD treatment markedly promoted platelet activation by releasing ATP level, increasing CD62P expression and PAC-1 binding, and decreasing cAMP level in platelets. Besides, PD increased phosphorylation of phosphoinositide 3-kinase (PI3K), protein kinase B (PKB or Akt), and glycogen synthase kinase 3β (GSK3β) in human platelets. Excitingly, PD-induced changes included platelet aggregation, a decrease of the cAMP content, and the increases of ATP, CD62P and PAC-1, which were significantly reversed by vorapaxar, which showed a similar function as thrombin. Conclusions: PD is an essential hemostatic ingredient in Panax notoginseng for promoting hematopoiesis and thrombopoiesis. PD induces platelet aggregation by affecting calcium signaling and activating PI3K/Akt/GSK3β signaling pathway, which could contribute to the new insight for the treatment of hemorrhagic disease.

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Effects of Momordica charantia exosomes on platelet activation, adhesion, and aggregation

Zhang

Wang

Liu³

et al. 2022

Blood Coagulation &Amp; Fibrinolysis

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The platelets play a crucial role in the progression of multiple medical conditions, such as stroke and tumor metastasis, where antiplatelet therapy may be a boon for treating these diseases. In this study, we have attempted to study the effects of extracted Momordica charantia exosomes (MCEs) on platelet activation, adhesion, and aggregation. Adult platelets isolated from healthy individuals were dose-dependently treated with MCEs (0.1, 40, and 200 μg/ml). We performed flow cytometry to detect the expression of platelet activation protein marker-activated GP IIb/IIIa (PAC-1) and P-selectin (CD62P). Platelet adhesion was analyzed through fluorescence labeling assays. The effect of MCEs on platelet-mediated cell migration of HCT116 cells was observed by transwell. Furthermore, the MCAO model of Sprague–Dawley rats was used to observe the effect of MCEs (200, 400, and 800 μg/kg) on platelet aggregation and maximum thrombotic agglutination in vivo. The results showed that 200 μg/ml MCEs exerted the most pronounced effect on platelet activation, adhesion, and aggregation. Experiments on animals showed that MCEs significantly inhibited platelet aggregation and attenuated the maximum thrombus agglutination. We concluded that MCEs inhibited platelet activation, adhesion, aggregation, and platelet-mediated migration of HCT116 cells, indicating the potential role MCEs may play in the treatment of stroke and tumor metastasis.

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Platelet Protease Activated Receptor 1 Is Involved in the Hemostatic Effect of 20(S)-Protopanaxadiol by Regulating Calcium Signaling

Abstract: in PPD-induced platelet aggregation by regulating calcium signaling. Collectively, our study could provide the new insights of PPD as an essential hemostatic ingredient in Panax notoginseng for the treatment of hemorrhagic disease.

Cited by 6 publications

References 61 publications

Hemostatic Effect of 20(S)-Panaxadiol by Induced Platelet Aggregation Depending on Calcium Signaling Pathway

Hemostatic Effect of 20(S)-Panaxadiol by Induced Platelet Aggregation Depending on Calcium Signaling Pathway

20(S)-Panaxadiol Enhances Hemostatic Effect on Activated Platelet by Affecting Calcium Signaling

Effects of Momordica charantia exosomes on platelet activation, adhesion, and aggregation

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