auraptene是植物中含量最丰富的香豆素衍生物。该化合物的药理价值已得到很好的证明,特别是在预防癌症和神经退行性疾病方面。血小板活化是导致动脉血栓形成的主要因素。因此,本研究评估了月桂烯对血小板聚集和血栓形成的影响。在仅用胶原蛋白刺激的人血小板中,金烯抑制血小板聚集。然而,在抑制凝血酶刺激的血小板聚集时,花生四烯酸,U46619Auraptene也抑制ATP释放,[Ca2+]i动员,和P-选择素表达。此外,它显著阻断PAC-1与整合素αIIbβ3的结合。然而,它对与整合素αIIbβ3介导的外内信号相关的特性没有影响,如粘附数,血小板的扩散区域,和纤维蛋白凝块收缩。Auraptene抑制Lyn-Fyn-Syk的磷酸化,磷脂酶Cγ2(PLCγ2),蛋白激酶C(PKC),Akt,和丝裂原活化蛋白激酶(MAPK;细胞外信号调节激酶(ERK1/2),和c-Jun氨基末端激酶(JNK1/2),但不是p38MAPK)。腺苷酸环化酶抑制剂SQ22536,也不是ODQ,鸟苷酸环化酶抑制剂,逆转了aulaptene介导的血小板聚集抑制。Auraptene降低了由二磷酸腺苷(ADP)引起的肺血栓栓塞引起的死亡率。总之,这项研究提供了明确的证据,表明auraptene是预防血栓栓塞性疾病的潜在治疗剂。
Auraptene is the most abundant coumarin derivative from plants. The pharmacological value of this compound has been well demonstrated, especially in the prevention of cancer and neurodegenerative diseases. Platelet activation is a major factor contributing to arterial thrombosis. Thus, this study evaluated the influence of auraptene in platelet aggregation and thrombotic formation. Auraptene inhibited platelet aggregation in human platelets stimulated with collagen only. However, auraptene was not effective in inhibiting platelet aggregation stimulated with thrombin, arachidonic acid, and U46619. Auraptene also repressed ATP release, [Ca2+]i mobilization, and P-selectin expression. Moreover, it markedly blocked PAC-1 binding to integrin αIIbβ3. However, it had no influence on properties related to integrin αIIbβ3-mediated outside-in signaling, such as the adhesion number, spreading area of platelets, and fibrin clot retraction. Auraptene inhibited the phosphorylation of Lyn-Fyn-Syk, phospholipase Cγ2 (PLCγ2), protein kinase C (PKC), Akt, and mitogen-activated protein kinases (MAPKs; extracellular-signal-regulated kinase (ERK1/2), and c-Jun N-terminal kinase (JNK1/2), but not p38 MAPK). Neither SQ22536, an adenylate cyclase inhibitor, nor ODQ, a guanylate cyclase inhibitor, reversed the auraptene-mediated inhibition of platelet aggregation. Auraptene reduced mortality caused by adenosine diphosphate (ADP)-induced pulmonary thromboembolism. In conclusion, this study provides definite evidence that auraptene signifies a potential therapeutic agent for preventing thromboembolic disorders.