• Biomedical Science Letters
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• v.25 no.4
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• pp.302-312
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• 2019

The aim of this work was to investigate the effect of black tea extract (BTE) on collagen -induced platelet aggregation. In this study, BTE (10~500 ㎍/mL) was shown to inhibit platelet aggregation via thromboxane A₂ (TXA₂) down-regulation by blocking cyclooxygenase-1 (COX-1) activity. Also, BTE decreased intracellular Ca²⁺ mobilization ([Ca²⁺]_i). Additionally, BTE enhanced the levels of both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are aggregation-inhibiting molecules. BTE inhibited the phosphorylation of phospholipase C (PLC) γ2 and syk activated by collagen. BTE regulated platelet aggregation via cAMP-dependent phosphorylation of vasodilator-stimulated phosphoprotein (VASP) Ser¹⁵⁷. The anti-platelet effects of BTE in high fat diet (HFD)-induced obese rats were evaluated. After eight weeks of BTE treatment (300 and 600 mg/kg), the platelet aggregation rate in the treated groups was significantly less than that in the HFD-fed control group. Also, BTE exhibited a hepatoprotective effect and did not exert hepatotoxicity. Therefore, these data suggest that BTE has anti-platelet effects on collagen-stimulated platelet aggregation and may have therapeutic potential for the prevention of platelet-mediated thrombotic diseases.

• YAKHAK HOEJI
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• v.41 no.3
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• pp.345-351
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• 1997

The purpose of this investigation was to determine the inhibition of $Na^+,\;K^+$-ATPase, cyclicAMP phophodiesterase and platelet activation by secondary metabolites isolated from mar ine organisms. The secondary metabolites were isolated and identified as six diterpenoids(1 : astrogorgin, 2 : ophirin, 3 : calicophirin B, 4, 5 and 6 : cladiellin) from the dichloromethane extract of Muricellajsp., four ceramides(1,2,3, and 4) from Acabaria undulata and three antharaquinones(1,2 : crysophanol, and 3 : physcion) from Urechis unicintus. The results demonstrated that diterpenoids(2,3, and 4) showed the inhibition of cyclicAMP phosphodiesterase, and ceramides(1,3, and 4) showed the inhibition of cyclicAMP phosphodiesterase and thrombin(0.1 units/ml)-induced aggregation of washed rabbit platelet, and anthrapuinones((1,2, and 3) showed the inhibition of $Na^+,\;K^+$-ATPase. Among the anthraquionones, 1,2-dimethoxy-3-methyl-8-hydroxy-anthraquinone(1) showed the inhibition of collagen(1.0 ${\mu}g$/ml)-induced aggregation in a concenration-dependent manner with IC50 value of 42.8 ${\mu}g$M.

• Biomedical Science Letters
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• v.25 no.2
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• pp.123-130
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• 2019

Platelet aggregation is essential for hemostatic process in case of blood vessels damages. However, excessive platelet aggregation can cause cardiovascular disorders including atherosclerosis, thrombosis and myocardial infarction. Scopoletin is usually found in the roots of genus Scopolia or Artemisia, and is known to have anticoagulant and anti-malarial effects. This study investigated the effect of scopoletin on human platelet aggregation induced by U46619, an analogue of thromboxane $A_2(TXA_2)$. Scopoletin had anti-platelet effects by down-regulating $TXA_2$ and intracellular $Ca^{2+}$ mobilization ($[Ca^{2+}]_i$), the aggregation-inducing molecules generated in activated platelets. On the other hand, scopoletin increased the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are known to be intracellular $Ca^{2+}$ antagonists. This resulted in inhibition of fibrinogen binding to ${\alpha}IIb/{\beta}_3$ in U46619-induced human platelet aggregation. In addition, scopoletin inhibited the release of adenosine trisphosphate (ATP) in dose-dependent manner. This result means that the aggregation amplification activity through the granule secretion in platelets was suppressed by scopoletin. Therefore, we demonstrated that scopoletin has a potent antiplatelet effect and is highly likely to prevent platelet-derived vascular disease.

• Journal of Ginseng Research
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• v.19 no.3
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• pp.206-211
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• 1995

This study was investigated to find the effects of petroleum ether extract (Lipophilic fraction) from Korean red ginseng on platelet aggregation and thrombin time of the plasma in two groups of the experimental rats. One group of rats were fed with 15% corn oil (15%kg-diet) containing a number of 18 : 2 (linoleic acid) or 15% beef-tallow (15%/kg-diet) containing saturated fatty acids for 3 weeks, and were followed by feeding the petroleum ether extract (25 mg/kg-diet) for 3 weeks. The other group of rats (control group) were fed with 15% corn oil or 15% beef-tallow for 6 weeks. The platelet aggregation induced by thrombin and collagen was significantly inhibited and the thrombin time was prolonged in the 15% corn oil plus petroleum ether extract administrated group than in the 15% corn oil administrated group. And the same results were shown in the 15% beef-tallow plus petroleum ether extract administrated group. These results suggest that the petroleum ether extract from Korean red ginseng may have the beneficial effects on the inhibition of the platelet aggregation and the inhibition of blood coagulation induced by dietary fats.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.221-226
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• 2023

Proper activation and aggregation of platelets are necessary, but excessive or abnormal aggregation can lead to cardiovascular diseases such as stroke, thrombosis, and atherosclerosis. Therefore, identifying a substance that can regulate or inhibit platelet aggregation is important for preventing and treating these diseases. Several studies have shown that certain ginsenoside compounds in Panax ginseng can inhibit platelet aggregation. Among these compounds, Rk3 (G-Rk3) from Panax ginseng needs to be further explored in order to reveal the mechanisms of action during inhibition. G-Rk3 significantly increased amounts of cyclic adenosine monophosphate (cAMP) and led to significant phosphorylation of cAMP-dependent kinase substrates vasodilator-stimulated phosphoprotein and inositol 1,4,5-trisphosphate receptor. Furthermore, the effect of G-Rk3 extended to the inhibition of PI3K/Akt phosphorylation resulting in the reduced secretion of intracellular granules. Ultimately, G-Rk3 effectively inhibited platelet aggregation. Therefore, we suggest G-Rk3's potential as a prophylactic or therapeutic agent for cardiovascular diseases caused by faulty platelet aggregation.

• Journal of Ginseng Research
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• v.47 no.6
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• pp.706-713
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• 2023

Background and objective: The ability to inhibit aggregation has been demonstrated with synthetically derived ginsenoside compounds G-Rp (1, 3, and 4) and ginsenosides naturally found in Panax ginseng 20(S)-Rg3, Rg6, F4, and Ro. Among these compounds, Rk3 (G-Rk3) from Panax ginseng needs to be further explored in order to reveal the mechanisms of action during inhibition. Methodology: Our study focused to investigate the action of G-Rk3 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, dense granule secretion, and thromboxane B₂ secretion. In addition, we checked the regulation of phosphorylation on PI3K/MAPK pathway, and thrombin-induced clot retraction was also observed in platelets rich plasma. Key Results: G-Rk3 significantly increased amounts of cyclic adenosine monophosphate (cAMP) and led to significant phosphorylation of cAMP-dependent kinase substrates vasodilator-stimulated phosphoprotein (VASP) and inositol 1,4,5-trisphosphate receptor (IP₃R). In the presence of G-Rk3, dense tubular system Ca²⁺ was inhibited, and platelet activity was lowered by inactivating the integrin αIIb/β₃ and reducing the binding of fibrinogen. Furthermore, the effect of G-Rk3 extended to the inhibition of MAPK and PI3K/Akt phosphorylation resulting in the reduced secretion of intracellular granules and reduced production of TXA₂. Lastly, G-Rk3 inhibited platelet aggregation and thrombus formation via fibrin clot. Conclusions and implications: These results suggest that when dealing with cardiovascular diseases brought upon by faulty aggregation among platelets or through the formation of a thrombus, the G-Rk3 compound can play a role as an effective prophylactic or therapeutic agent.

• Toxicological Research
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• v.16 no.4
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• pp.311-315
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• 2000

Previous studies showed that benzoquinone derivatives inhibited platelet aggregation. but there is no information available on their cytotoxicity to platelets. 1n the present study. washed platelets isolated from rats were treated with 1.4-benzoquinone. a representative benzoquinone derivative. to examine its antiaggregating effect and cytotoxicity. 1.4-Benzoquinone significantly inhibited thrombin-induced platelet aggregation. Consistent with this finding. 1.4-benzoquinone suppressed cytosolic calcium increase induced by thrombin. To examine the cytotoxicity by 1 A-benzoquinone in platelets. turbidometry and lactate dehydrogenase release were measured. Treatment with 1.4-benzoquinone resulted in slight cytotoxicity (30% release at 60 min) to platelets. However. the cytotoxicity was not correlated with increase of cytosolic calcium levels in platelets. All these data suggested that 1.4-benzoquinone inhibited thrombin-induced platelet aggregation mediated by inhibition elf calcium level increase and that 1.4-benzoquinone reveals cytotoxicity to some extent without alteration of calcium level in platelets.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.271.3-272
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• 2003

Rhus verniciflua Stokes (RVS) is a widely used herbal plant with various biological properties. Our previous study using in vitro platelet aggregation in whole blood showed that the fractions of RVS had strong anti-aggregatory activity. In this study, using in vitro platelet aggregation in PRP and coagulation parameters, to investigate the anti-platelet activity and anticagulant effects of RVS ethyl acetate layer, the layer was subsequently fractionated by ODS columm chromatograph (50％ MeOH). (omitted)

• The Journal of Internal Korean Medicine
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• v.31 no.4
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• pp.714-721
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• 2010

Objective : The study was designed to test the anti-platelet effect of the extract Cheongpyesagan-tang and compare it with aspirin in vitro. Methods : The extract from Cheongpyesagan-tang was made by the pharmacy department of Kyung Hee Oriental Medical Hospital. The extract was investigated for inhibition against the collagen induced aggregation of human platelet suspensions on aggregometry. Aspirin and aspirin-Cheongpyesagan-tang were investigated together. Results : 1. In collagen induced human platelet aggregation test, the extract from Cheongpyesagan-tang significantly inhibited in concentration 30mg/ml (p<0.05), 40mg/ml, 50mg/ml (p<0.001) and the effect depended on concentration over 20mg/ml. 2. Aspirin and aspirin-Cheongpyesagan-tang inhibited collagen induced human platelet aggregation significantly (p<0.001). Aspirin-extract of Cheongpyesagan-tang inhibition rate was higher than aspirin only (p<0.05). Conclusions : The extract of Cheongpyesagan-tang has anti-platelet aggregation and synergic effect with aspirin on human platelet in vitro.

• Food Science and Biotechnology
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• v.16 no.2
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• pp.218-222
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• 2007

The anticoagulant properties of Cinnamomum cassia bark-derived materials were evaluated against platelet aggregation induced by arachidonic acid (AA), collagen, platelet activating factor (PAF), or thrombin, and these effects were then compared to those of three commercially available compounds (cinnamic acid, cinnamyl alcohol, and aspirin). The active constituent obtained from C. cassia barks was isolated by silica gel column chromatography and high pressure liquid chromatography (HPLC), and was characterized as trans-cinnamaldehyde by MS, $^1H-NMR$, $^{13}C-NMR$, and IR spectroscopy. With regard to 50% inhibitory concentration ($IC_{50}$) values, cinnamaldehyde was found to effectively inhibit platelet aggregation induced by AA ($IC_{50},\;43.2\;{\mu}M$) and collagen ($IC_{50},\;3.1\;{\mu}M$). By way of comparison, cinnamaldehyde proved to be a significantly more potent platelet inhibitor against platelet aggregation induced by collagen than aspirin. The effect exerted by cinnamaldehyde against platelet aggregation induced by AA was 1.2 times less than that of aspirin. These results indicate that cinnamaldehyde may prove useful as a lead compound for the inhibition of platelet aggregation induced by AA and collagen.