• 대한의생명과학회지
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• 제25권4호
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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.

• 약학회지
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• 제41권3호
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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.

• 대한의생명과학회지
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• 제25권2호
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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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• 제19권3호
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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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• 제66권
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• pp.221-226
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• 2023

혈소판의 적절한 활성화와 응집이 필요하지만 과도하거나 비정상적인 응집은 뇌졸중, 혈전증, 동맥경화증과 같은 심혈관 질환을 유발할 수 있다. 따라서 이러한 질병을 예방하고 치료하기 위해서는 혈소판 응집을 조절하거나 억제할 수 있는 물질을 찾는 것이 중요하다. 여러 연구에서 Panax 인삼의 특정 ginsenoside 화합물이 혈소판 응집을 억제할 수 있음이 알려져 있다. 이들 화합물 중 Panax ginseng의 Rk3 (G-Rk3)는 혈소판 응집 억제의 기전이 불확실 하기에 이를 밝히기 위한 연구가 필요하다. G-Rk3는 cAMP의 양을 강하게 증가시켰고 cAMP 의존성 kinase의 기질인 VASP 및 IP3R의 인산화를 유도했다. 또한, G-Rk3의 효과는 PI3K/Akt 인산화의 억제를 일으켜 세포 내 과립의 분비를 감소시켰다. 궁극적으로 G-Rk3는 혈소판 응집을 효과적으로 억제하였다. 따라서 우리는 과도한 혈소판 응집으로 인한 심혈관 질환의 예방 또는 치료제로서의 G-Rk3의 가능성을 제안한다.

• Journal of Ginseng Research
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• 제47권6호
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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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• 제16권4호
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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.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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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)

• 대한한방내과학회지
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• 제31권4호
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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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• 제16권2호
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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.