• Journal of Ginseng Research
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• v.40 no.4
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• pp.359-365
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• 2016

Background: Glycoprotein IIb/IIIa (${\alpha}aIIb/{\beta}_3$) is involved in platelet adhesion, and triggers a series of intracellular signaling cascades, leading to platelet shape change, granule secretion, and clot retraction. In this study, we evaluated the effect of ginsenoside Ro (G-Ro) on the binding of fibrinogen to ${\alpha}aIIb/{\beta}_3$. Methods: We investigated the effect of G-Ro on regulation of signaling molecules affecting the binding of fibrinogen to ${\alpha}aIIb/{\beta}_3$, and its final reaction, clot retraction. Results: We found that G-Ro dose-dependently inhibited thrombin-induced platelet aggregation and attenuated the binding of fibrinogen to ${\alpha}aIIb/{\beta}_3$ by phosphorylating cyclic adenosine monophosphate (cAMP)-dependently vasodilator-stimulated phosphoprotein (VASP; $Ser^{157}$). In addition, G-Ro strongly abrogated the clot retraction reflecting the intensification of thrombus. Conclusion: We demonstrate that G-Ro is a beneficial novel compound inhibiting ${\alpha}aIIb/{\beta}_3$-mediated fibrinogen binding, and may prevent platelet aggregation-mediated thrombotic disease.

• Natural Product Sciences
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• v.26 no.4
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• pp.295-302
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• 2020

Cudrania tricuspidata (C. tricuspidata) is a deciduous tree found in Japan, China and Korea. The root, stems, bark and fruit of C. tricuspidata has been used as traditional herbal remedies such as eczema, mumps, acute arthritis and tuberculosis. In this study, we investigated the potential efficacies of this natural compound by focusing on the inhibitory effect of cudraxanthone L (CXL) isolated from the roots of C. tricuspidata on human platelet aggregation. Our study focused on the action of CXL on collagen-stimulated human platelet aggregation, inhibition of platelet signaling molecules such as fibrinogen binding, intracellular calcium mobilization, fibronectin adhesion, dense granule secretion, and thromboxane A2 secretion. In addition, we investigated the inhibitory effect of CXL on thrombin-induced clot retraction. Our results showed that CXL inhibited collagen-induced human platelet aggregation, intracellular calcium mobilization, fibrinogen binding, fibronectin adhesion and clot retraction without cytotoxicity. Therefore, we confirmed that CXL has inhibitory effects on human platelet activities and has potential value as a natural substance for preventing thrombosis.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.171-178
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• 2023

Morus alba, a popular medicinal plant belonging to the family Moraceae, has long been used commonly in traditional medicine and has various physiological activities, including antidiabetic, anti-microbial, diuretic, anti-oxidant, and anti-cancer activities. Morusinol was isolated from the root bark of M. alba; however, its biological effects have not yet been reported. Therefore, we examined the inhibitory effects of morusinol on human platelet aggregation, Ca²⁺ mobilization, and αIIb/β₃ activity. Our data showed that collagen-induced human platelet aggregation was inhibited by morusinol without cytotoxicity. In this study, we examined whether morusinol inhibits platelet aggregation through the regulation of integrin αIIb/β₃ and its associated signaling molecules. We observed that morusinol inhibited αIIb/β₃ activation by regulating vasodilator-stimulated phosphoprotein, phosphatidylinositol-3 kinase, Akt (protein kinase B), and glycogen synthase kinase-3α/β. These results show that morusinol inhibited fibronectin adhesion, fibrinogen binding, and clot retraction. Taken together, morusinol shows strong antiplatelet and anti-clot retraction effects and is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

• Journal of Chest Surgery
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• v.2 no.1
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• pp.105-114
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• 1969

This experiment was carried out to study the responses of cellular component of blood and bone marrow to cold and also the changes of coagulation during cooling. Forty-two mongrel dogs were subjected to hypothermia by ice-water surface cooling technique. Lowest body temperature ranged from 21-23 degree. Dogs were divided into 3 groups,Group I, 12 dogs: pentothal anesthesia for 3 hours, Group II, 20 dogs;hypothermic group and Group III,10 dogs;postsplenectomy hypothermic group. Results were summarized as follows: 1. Hemoglobin, hematocrit and red blood cell count significantly increased when animals were cooled, and increase was noted in similar magnitude among the animals of Group I. 2. White blood cell count extremely decreased after cooling and effect of splenectomy on white blood cell count was not apparent. No significant changes were seen among Group I. 3. Differential count of white blood cell when cooled showed relative increase of polymorphonuclear neutrophil and decrease of lymphocyte. 4. There was marked decrease of platelets when body temperature reached to 21-23degree and essentially. no changes was noted in Group I. 5. Clotting time, bleeding time, plasma prothrombin time, recalcification time, and fibrinolysis showed no significant changes when dogs were cooled. Clot retration and prothrombin consumption during hypothermia appeared to be poor. In Group II, bleeding time decreased after splenctomy and when body temperature was lowered, plasma prothrombin time, clot retraction, and prothrombin consumption decreased. Decreased bleeding time and poor clot retraction were noted in Group I. 6. It was found that megacaryocyte count decreased even though platelet count of peripheral blood markedly diminsished when animals were cooled. There was some tendency of erythroid hyperplasia noted during hypothermia.

• Korean Journal of Veterinary Research
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• v.28 no.1
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• pp.193-198
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• 1988

Blood coagulation time, bleeding time, clot retraction ability, thrombocytes counts and hematological values under electroacpuncture anesthesis and medicament anesthesia, using 10 mongrel dogs were compared. The results were summarized as follows: 1. Blood coagulation time under electroacupuncture anesthesia was shorter than that under medicament anesthesia (p<0.001). 2. Bleeding time under electroacupuncture anesthesia was shorter than that under medicament anesthesia (p<0.01). 3. Clot retraction ability under electroacupuncture anesthesia was better than that under medicament anesthesia (p<0.01). 4. Thrombocytes counts under electroacupuncture anesthesia was more increased than that under medicament anesthesia (p<0.05). 5. Erythrocytes counts, hematocrit values, hemnglobin contents and leukocytes counts were decreased (p<0.01) under medicament anesthesia in comparison with control group, but there was no significant difference under electroacupuncture anesthesia.

• Journal of Applied Biological Chemistry
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• v.63 no.4
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• pp.339-345
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• 2020

Euchrestaflavanone A (EFA) is a flavonoid found in the root bark of Cudrania tricuspidata. C. tricuspidata extract, widely used throughout Asia in traditional medicine, has been investigated phytochemically and biologically and is known to have anti-obesity, anti-inflammatory, and anti-tumor effects. It has been reported that C. tricuspidata extract also possesses anti-platelet effects; however, the mechanism of its anti-platelet and anti-thrombotic activities is yet to be elucidated. In this study, we investigated the effects of EFA on the modulation of platelet function using collagen-induced human platelets. Our results showed that EFA markedly inhibited platelet aggregation. Furthermore, it downregulated glycoprotein IIb/IIIa (αIIb/β3)-mediated signaling events, including platelet adhesion, granule secretion, thromboxane A2 production, and clot retraction, but upregulated the cyclic adenosine monophosphate-dependent pathway. Taken together, EFA possesses strong anti-platelet and anti-thrombotic properties and is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

• Korean Journal of Pharmacognosy
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• v.51 no.4
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• pp.231-237
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• 2020

Euchrestaflavanone B (EFB) is a flavonoid that can be found in root bark, particularly in Cudrania tricuspidata (C. tricuspidata). The extract of C. tricuspidata is widespread throughout Asia and used in traditional medicine. In a previous study, we found anti-platelet effects of substances isolated from C. tricuspidata on collagen-induced human platelets. However, the C. tricuspidata still contains numerous substances, thus, we have searched new candidate, EFB isolated from C. tricuspidata for anti-platelet effect. Our results showed that EFA inhibited collagen-induced platelet aggregation and glycoprotein IIb/IIIa (αIIb/β3)-mediated signaling events, including platelet adhesion, granule secretion, thromboxane A2 production and clot retraction. These results suggest that EFA has inhibitory effects on human platelet activities and thrombus formation and has potential value as a natural substance for preventing platelet-induced thrombosis.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.455-461
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• 2023

Glycyrrhiza glabra is a well-known medicinal herb that grows in various parts of the world and glabridin is a major chemical compound that is found in the root extract of Glycyrrhiza glabra. Glabridin is a natural compound known to have antioxidant, anti-inflammatory, anti-atherogenic, anti-osteoporotic and skin-whitening. In this study, we investigated if glabridin inhibited platelet aggregation and thrombus formation. We observed that glabridin inhibited collagen-induced platelet aggregation and suppressed signal transduction molecules such as phosphatidylinositol-3 kinase (PI₃K), Akt, glycogen synthase kinase-3α/β (GSK-3α/β), SYK, cytosolic phospholipase A₂, and p38 expression. In addition, glabridin suppressed thromboxane A₂ generation and thrombin-induced clot retraction. Taken together, glabridin showed strong antiplatelet effects and may be used to block thrombosis- and platelet-mediated cardiovascular diseases.

• Journal of Ginseng Research
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• v.40 no.1
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• pp.76-85
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• 2016

Background: Binding of adhesive proteins (i.e., fibrinogen, fibronectin, vitronectin) to platelet integrin glycoprotein IIb/IIIa (${\alpha}IIb/{\beta}3$) by various agonists (thrombin, collagen, adenosine diphosphate) involve in strength of thrombus. This study was carried out to evaluate the antiplatelet effect of total saponin from Korean Red Ginseng (KRG-TS) by investigating whether KRG-TS inhibits thrombin-induced binding of fibrinogen and fibronectin to ${\alpha}IIb/{\beta}3$. Methods: We investigated the effect of KRG-TS on phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and dephosphorylation of phosphatidylinositol 3-kinase (PI3K) and Akt, affecting binding of fibrinogen and fibronectin to ${\alpha}IIb/{\beta}3$, and clot retraction. Results: KRG-TS had an antiplatelet effect by inhibiting the binding of fibrinogen and fibronectin to ${\alpha}IIb/{\beta}3$ via phosphorylation of VASP ($Ser^{157}$), and dephosphorylation of PI3K and Akt on thrombin-induced platelet aggregation. Moreover, A-kinase inhibitor Rp-8-Br-cyclic adenosine monophosphates (cAMPs) reduced KRG-TS-increased VASP ($Ser^{157}$) phosphorylation, and increased KRG-TS-inhibited fibrinogen-, and fibronectin-binding to ${\alpha}IIb/{\beta}3$. These findings indicate that KRG-TS interferes with the binding of fibrinogen and fibronectin to ${\alpha}IIb/{\beta}3$ via cAMP-dependent phosphorylation of VASP ($Ser^{157}$). In addition, KRG-TS decreased the rate of clot retraction, reflecting inhibition of ${\alpha}IIb/{\beta}3$ activation. In this study, we clarified ginsenoside Ro (G-Ro) in KRG-TS inhibited thrombin-induced platelet aggregation via both inhibition of $[Ca^{2+}]_i$ mobilization and increase of cAMP production. Conclusion: These results strongly indicate that KRG-TS is a beneficial herbal substance inhibiting fibrinogen-, and fibronectin-binding to ${\alpha}IIb/{\beta}3$, and clot retraction, and may prevent platelet ${\alpha}IIb/{\beta}3$-mediated thrombotic disease. In addition, we demonstrate that G-Ro is a novel compound with antiplatelet characteristics of KRG-TS.

• Journal of Ginseng Research
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• v.45 no.4
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• pp.490-497
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• 2021

Background and objective: Synthetic ginsenoside compounds G-Rp (1,3, and 4) and natural ginsenosides in Panax ginseng 20(S)-Rg3, Rg6, F4 and Ro have inhibitory actions on human platelets. However, the inhibitory mechanism of ginsenoside Rk1 (G-Rk1) is still unclear thus, we initiated investigation of the anti-platelet mechanism by G-Rk1 from Panax ginseng. Methodology: Our study focused to investigate the action of G-Rk1 on agonist-stimulated human platelet aggregation, inhibition of platelet signaling molecules such as fibrinogen binding with integrin α_IIbβ₃ using flow cytometry, intracellular calcium mobilization, fibronectin adhesion, dense granule secretion, and thromboxane B2 secretion. Thrombin-induced clot retraction was also observed in human platelets. Key Results: Collagen, thrombin, and U46619-stimulated human platelet aggregation were dose-dependently inhibited by G-Rk1, while it demonstrated a more effective suppression on collagen-stimulated platelet aggregation using human platelets. Moreover, G-Rk1 suppressed collagen-induced elevation of Ca²⁺ release from endoplasmic reticulum, granule release, and α_IIbβ₃ activity without any cytotoxicity. Conclusions and implications: These results indicate that G-Rk1 possess strong anti-platelet effect, proposing a new drug candidate for treatment and prevention of platelet-mediated thrombosis in cardiovascular disease.