• BMB Reports
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• v.31 no.5
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• pp.515-518
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• 1998

Adhesive interaction of the platelet glycoprotien IIb-IIIa (GP IIb-IIIa) with a plasma protein, such as fibrinogen, plays an important role in thrombosis and hemostasis. The specific sequence Arg-Gly-Asp (RGD) is critical for the binding of fibrinogen to platelet. To examine and characterize the GP IIb-IIIa antagonist from natural sources, we have developed a simple enzyme-linked immunosorbant assay (ELISA) system. The GP IIb-IIIa complex was purified to homogeneity from platelet Iysates by the combination of two affinity chromatographic methods using the synthetic RGD peptide (GRGDSPK)-immobilized Sepharose and wheat germ lectin-Sepharose. The synthetic peptide GRGDSP inhibits GP IIb-IIIa binding to immobilized fibrinogen with an $IC_{50}$ of $1.5\;{\mu}M$. Venoms of three different snake species and a Korean scolopendra extract have strong antagonistic activities for the binding of human fibrinogen to the platelet GP IIb-IIIa complex. The $IC_{50}$ values of the snake venom s and scolopendra were in the range of $5.5\;{\mu}g$ to $60\;{\mu}g$. These results provide meaningful information for developing antiplatelet agents.

• Journal of the Korean Society of Radiology
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• v.13 no.3
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• pp.359-369
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• 2019

To evaluate the effect of simultaneous use of platelet glycoprotein IIb / IIIa receptor blocker and catheter assisted thrombus aspiration in the treatment of coronary stent thrombosis. 267 patients ($64.6{\pm}12.1years$, 187 men) with stent thrombosis on coronary angiography at Chonnam National University Hospital from July 2008 to July 2017 were enrolled. We devided two groups based on treatment modalities: Group I (N=32, platelet glycoprotein IIb / IIIa receptor blocker and thrombo-aspiration), Group II (N =235, either platelet glycoprotein IIb /IIIa receptor blocker or thrombo-aspiration, or none of both), and the major cardiac events including death, revascularization and stent thrombosis were followed up for 1 year. There were no significant differences in clinical characteristics between the two groups including age (Group I: $60.8{\pm}12.9$ vs. Group II: $65.1{\pm}11.9$, p= 0.603), male (Group I: 75.0% vs. Group II: 69.4%, p=0.681), and left ventricular ejection fraction (Group I: $58.1{\pm}9.0%$ vs. Group II: $59.5{\pm}11.9%$, p= 0.127). The major cardiac events did not differ between the two groups (Group I: 12.5% vs. Group II: 23.8%, p=0.180). The secondary endopoints were as followings: The mortality rate (Group I: 0% vs. 13.2%, Group II: p=0.034), target lesion revascularization (Group I: 9.4% vs Group II: 6.4%, p=0.461) and stent thrombosis (Group I: 3.1% vs. Group II: 4.7%, p=1.000). In conclusion, in the treatment of coronary artery stent thrombosis, simultaneous use of platelet glycoprotein IIb / IIIa receptor blocker and thrombus aspiration was associated with better clinical outcomes regarding 1 year mortality.

• Journal of Applied Biological Chemistry
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• v.61 no.3
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• pp.257-265
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• 2018

The Panax ginseng Mayer is used in conventional medicine in Asia owing to its preventing effects on thrombosis, hypertension, atherosclerosis, vasorelaxation and myocardial infarction. Because platelets are crucial mediators of cardiovascular diseases, many studies have investigated its functions. The previous study showed the antiplatelet effects of crude ginseng fraction and two of its components, ginsenoside Rg3 (20S and 20R). In addition, ginsenoside Rg3-enriched fraction shows an inhibitory effect on collagen-activated rat platelets. However, the mechanism underlying this effect remains unclear. Thus, I investigated the inhibitory action of ginsenoside Rg3 (20S, G-Rg3) on the regulation of signaling molecules involved in ${\alpha}IIb/{\beta}_3$ activation. I found that G-Rg3, in a cyclic AMP dependent manner, inhibited thrombin-induced activation of human platelets and affinity of fibrinogen and fibronectin with ${\alpha}IIb/{\beta}_3$. Thus, in the present study, G-Rg3 showed an inhibitory effect on glycoprotein IIb/IIIa (${\alpha}IIb/{\beta}_3$) activation, suggesting its potential use for preventing platelet-mediated thrombotic disease.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.236-243
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• 2023

Platelets act a fundamental role in primary- and secondary-hemostasis, however, platelet activation may cause thrombosis simultaneously. Therefore, control of platelet aggregation is crucial in preventing thrombosis-mediated diseases. Recently, the development of insect materials is attracting attention. Among the highly nutritious functional food sources, insects such as two-spotted cricket (Gryllus bimaculatus). Gryllus bimaculatus (G. bimaculatus) contains high protein and unsaturated fatty acids and has been registered as a food material September 2015 by the Ministry of Food and Drug Safety of Korea. In this study, we examined whether G. bimaculatus extract (GBE) inhibits platelet aggregation, intracellular calcium mobilization, thromboxane A₂ production and glycoprotein IIb/IIIa (integrin αIIb/β3) activation. We investigated whether GBE can regulate signaling molecules, such as 1, 4, 5-triphosphate receptor type I, extracellular signal-regulated kinase, cytosolic phospholipase A₂, mitogen-activated protein kinases p38, vasodilator-stimulated phosphoprotein, phosphatidylinositol-3 kinase, Akt, glycogen synthase kinase-3α/β, and SYK. Taken together, GBE 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.

• Biomolecules & Therapeutics
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• v.23 no.1
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• pp.60-70
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• 2015

In this study, we investigated the effects of cordycepin-enriched (CE)-WIB801C, a n-butanol extract of Cordyceps militaris-hypha on collagen-stimulated platelet aggregation. CE-WIB801C dose dependently inhibited collagen-induced platelet aggregation, and had a synergistic effect together with cordycepin (W-cordycepin) from CE-WIB801C on the inhibition of collagen-induced platelet aggregation. CE-WIB801C and cordycepin stimulated the phosphorylation of VASP ($Ser^{157}$) and the dephosphorylation of PI3K and Akt, and inhibited the binding of fibrinogen to glycoprotein IIb/IIIa (${\alpha}IIb/{\beta}3$) and the release of ATP and serotonin in collagen-induced platelet aggregation. A-kinase inhibitor Rp-8-Br-cAMPS reduced CE-WIB801C-, and cordycepin-increased VASP ($Ser^{157}$) phosphorylation, and increased CE-WIB801C-, and cordycepin-inhibited the fibrinogen binding to ${\alpha}IIb/{\beta}3$. Therefore, we demonstrate that CE-WIB801C-, and cordycepin-inhibited fibrinogen binding to ${\alpha}IIb/{\beta}3$are due to stimulation of cAMP-dependent phosphorylation of VASP ($Ser^{157}$), and inhibition of PI3K/Akt phosphorylation. These results strongly indicate that CE-WIB801C and cordycepin may have preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

• 대한임상약리학회:학술대회논문집
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• 1998.12a
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• pp.44-44
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• 1998

• YAKHAK HOEJI
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• v.51 no.3
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• pp.186-193
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• 2007

This study was performed to analyse the economic value of abciximab which is used in PCI to prevent high-risk patients with ischemic complications. The effectiveness of abciximab was extracted from published clinical trials by search-ing CCIS, and the direct medical costs relevant to using abciximab were estimated from the NHI claims database. The results in terms of cost per life-year gained (LYG) and cost per QALY gained showed that abciximab was cost-effective enough to deserve its cost. Social net benefit resulting from abciximab in PCI was estimated to be 60-70 billion Won per year.

• 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.

• Korean Journal of Pharmacognosy
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• v.51 no.2
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• pp.100-106
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• 2020

The extract of Cudrania tricuspidata is used in ethnomedicine throughout Eastern Asia in China, Korea and Japan. In Korean traditional medicine, Cudrania tricuspidata has been used to treat eczema, mumps, tuberculosis, contusions, insomnia and acute arthritis. In addition, it has been reported that root extract of Cudrania tricuspidata has anti-platelet effects. Therefore, we investigated which compound in Cudrania tricuspidata has inhibitory effect on platelet aggregation. In this study, we tried to explain the inhibitory mechanism of steppogenin from Cudrania tricuspidata on human platelet aggregation. Collagen-induced human platelet aggregation and [Ca²⁺]_i mobilization were dose-dependently inhibited by steppogenin and we determined the inhibition by steppogenin is due to the down regulation of extracellular-signal-regulated kinase(ERK) and inositol-1,4,5-triphosphate receptor type I(IP₃RI) phosphorylation. In addition, steppogenin inhibited collagen-induced fibronectin adhesion to αIIb/β3 and thromboxane A₂ generation. Thus, in the present study, steppogenin showed an inhibitory effect on human platelet aggregation, suggesting its potential use for preventing platelet-induced cardiovascular disease.