• BMB Reports
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• 제31권5호
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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.

• 한국방사선학회논문지
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• 제13권3호
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• pp.359-369
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• 2019

관상동맥 스텐트 혈전증 치료에 있어서 혈소판 당단백 IIb/IIIa 수용체 차단제와 카테터를 이용한 혈전 흡입술을 동시에 시행한 경우의 효과에 대하여 알아보고자 하였다. 2008년 07월부터 2017년 07월까지의 일대학교병원 심혈관센터에서 경피적 관상동맥 스텐트 삽입술 후 관상동맥 조영술에서 스텐트 혈전증이 발생한 환자 267명($64.6{\pm}12.1$년, 187남자) 그룹 I(혈전용해술과 혈전흡입술 동시 시행한 경우, n=32명), 그룹 II(혈전용해술이나 혈전흡입술 한 가지만 시행한 경우 혹은 둘 다 시행하지 않은 경우, n=235명)로 분류하여 주요심장사건, 사망 발생률, 표적병변 재개통술 그리고 스텐트 혈전 등을 1 년동안 추적 관찰하였다. 두 군간에 임상 특성에서 연령(그룹I: $60.8{\pm}12.9$ vs. 그룹II: $65.1{\pm}11.9$, p=0.603), 남성(그룹I: 75.0% vs. 그룹II: 69.4%, p=0.681), 좌심실구혈율(그룹I: $58.1{\pm}9.0$ vs. 그룹II: $59.5{\pm}11.9$, p=0.127)등 양군 간에 차이는 없었다. 주요 심장사건은 두 군간에 차이를 보이지 않았으나(그룹I: 12.5% vs. 그룹II: 23.8%, p=0.180), 세부적으로 살펴보면 사망발생률(그룹I: 0% vs. 그룹II: 13.2%, p=0.034), 표적병변 재개통술(그룹I: 9.4% vs. 그룹II: 6.4%, p=0.461) 그리고 스텐트 혈전증(그룹I: 3.1% vs. 그룹II: 4.7%, p=1000)으로, 사망발생률은 혈소판 당단백 IIb/IIIa 수용체 차단제와 혈전흡입술을 동시에 시행한 군에서 유의하게 낮았다. 결론적으로, 관상동맥 스텐트 혈전증 치료에 있어 혈전용해술과 혈전흡입술을 동시 시행하는 경우에 비교군보다 사망 발생율을 감소시켰다.

• Journal of Applied Biological Chemistry
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• 제61권3호
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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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• 제66권
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• pp.236-243
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• 2023

혈소판은 1차 및 2차 지혈에서 근본적인 역할을 하는 세포지만 혈소판의 과도한 활성화는 혈전증을 유발할 수 있다. 따라서 혈소판 응집의 적절한 조절은 혈전증 매개 질환을 예방하는 데 중요하다. 최근 곤충소재의 개발이 주목을 받고 있다. 다양한 곤충 자원 중 고영양 기능성 식품원으로는 쌍별귀뚜라미(Gryllus bimaculatus)와 같은 곤충류가 있다. 쌍별귀뚜라미 는 고단백 및 불포화지방산을 함유하고 있으며 2015년 9월 식품의약품안전처로부터 식품원료로 등록되었다. 본 연구에서는 쌍별귀뚜라미 에탄올 추출물(G. bimaculatus extract)이 혈소판 응집, 세포 내 Ca²⁺ 조절, thromboxane A₂ 생산 및 glycoprotein IIb/IIIa (integrin αIIb/β3) 활성화를 억제하는지 여부를 확인하고. 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 및 SYK 같은 신호 분자를 조절할 수 있는지 여부를 조사했다. 우리는 쌍별귀뚜라미 추출물이 혈소판 관련 혈전증 및 심혈관 질환을 예방할 수 있는 잠재적인 치료 약물로 가치가 있음을 규명하였다.

• 생약학회지
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• 제51권4호
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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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• 제23권1호
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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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• 대한임상약리학회 1998년도 제7차 추계학술대회 및 정기총회
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• pp.44-44
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• 1998

• 약학회지
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• 제51권3호
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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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• 제40권1호
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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.

• 생약학회지
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• 제51권2호
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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.