U46619-유도의 혈소판 활성화 억제를 통한 Esculetin의 혈전 생성억제 효과

국문 초록 (Abstract)

Esculetin은 coumarin계 생리활성 6,7-디하이드록시 유도체로서 비만, 당뇨병, 신부전 및 CVD에 대한 약리학적 활성이 있음이 알려져 있다. 어떤 연구에서는 사람 혈소판 활성화 및 실험적 마우스 모델에서 esculetin의 효과를 확인했으며, esculetin이 세척된 사람 혈소판에서 collagen 및 arachidonic acid로 유도한 혈소판 응집을 억제한 것으로 보고하였다. 그러나 thrombin 및 U46619와 같은 다른 작용제에는 효과가 없는 것으로 확인되었으며, esculetin이 어떤 기전으로 항혈소판 및 항혈전 효과를 가지는지 명확히 밝혀지지 않았다. 본 연구에서는 thromboxane A2의 유사체 중 하나인 U46619(9,11-dideoxy 9a,11a-methanoepoxy prostaglandin F2a)에 의해 유도된 사람 혈소판을 사용하여 esculetin이 혈소판 기능 조절에 미치는 영향을 조사하였다. 그 결과 U46619를 자극유도제로 처리했을 때 혈소판 활성화가 일어났고 U46619에 의해 세포질 내 칼슘 동원과 fibrinogen binding이 증가했다. 그러나 esculetin은 cyclic nucleotides를 상향 조절하였고, 세포질 내 칼슘 동원, 당단백질 Ⅱb/Ⅲa(αⅡb/β3) 매개의 fibrinogen binding 및 혈전 수축을 농도 의존적으로 하향 조절하였다. 따라서 esculetin이 강력한 항혈소판 및 항혈전 특성을 갖고 있으며, 혈소판 관련 혈전증 및 심혈관 질환을 예방할 수 있는 잠재적인 치료 약물 후보가 될 수 있음을 제안한다.

다국어 초록 (Multilingual Abstract)

Esculetin, a bioactive 6,7-dihydroxy derivative of coumarin, displays pharmacological activity against obesity, diabetes, renal failure, and cardiovascular diseases (CVDs). It has been reported that esculetin inhibits collagen and arachidonic acid-induced platelet aggregation in washed human platelets. However, there are no effects on other agonists such as thrombin and U46619, and its mechanism of action has not been completely elucidated. This study investigated the effects of esculetin on the modulation of platelet function using human platelets induced by the agonist U46619 (9,11-dideoxy 9a,11a-methanoepoxy prostaglandin F2a), which is one of the analogues of thromboxane A2. U46619 activates platelets, and increases intracellular calcium mobilization and fibrinogen binding. However, esculetin upregulated the cyclic nucleotides and downregulated intracellular calcium mobilization, glycoprotein Ⅱb/Ⅲa (αⅡb/β₃)-mediated fibrinogen binding, and clot retraction, dose-dependently. In conclusion, esculetin has demonstrated potent antiplatelet and antithrombotic properties, making it a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

목차 (Table of Contents)

• ABSTRACT
• 서론
• 재료 및 방법
• 결과 및 고찰
• 요약
• REFERENCES

참고문헌 (Reference)

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