Platycodin D inhibits platelet function and thrombus formation through inducing internalization of platelet glycoprotein receptors.
Platycodin D inhibits platelet function and thrombus formation through inducing internalization of platelet glycoprotein receptors.
复制标题
Platycodin D 通过诱导血小板糖蛋白受体内化来抑制血小板功能和血栓形成
DOI：
10.1186/s12967-018-1688-z
复制
发表时间：
2018-11-15
影响因子：
7.4
通讯作者：
Qiao J
中科院分区：
文献类型：
--
作者：
Luo Q;Wei G;Wu X;Tang K;Xu M;Wu Y;Liu Y;Li X;Sun Z;Ju W;Qi K;Chen C;Yan Z;Cheng H;Zhu F;Li Z;Zeng L;Xu K;Qiao J
背景桔梗皂苷D(Platycodin D，PD)是桔梗根部的主要生物活性成分之一，具有抗病毒、抗炎、抗癌等多种生物学和药理活性。然而，它是否影响血小板功能仍不清楚。本研究旨在评价PD在血小板功能和血栓形成中的作用。方法用PD处理血小板，检测血小板聚集、活化、铺展、凝块回缩、糖蛋白受体表达。结果桔梗皂苷D可显著抑制胶原、二磷酸腺苷、花生四烯酸和肾上腺素诱导的小鼠血小板聚集，降低血小板P-选择素表达、整合素αIIbβ3活性、纤维蛋白原扩散和凝块回缩，并降低胶原相关肽和凝血酶刺激的血小板中Syk和PLCγ2的磷酸化水平。此外，经PD处理的小鼠血小板在体内止血和动脉血栓形成方面明显受损。有趣的是，PD诱导糖蛋白受体αIIbβ3、GPIBα和GPVI内化。但GM6001、细胞松弛素D、BAPTA-AM和Wortmannin均不能阻止PD诱导的受体内化。结论PD可抑制血小板聚集、活化，损害止血和动脉血栓形成，提示PD可能是一种有效的抗血栓药物。
BackgroundPlatycodin D (PD) is one of the major bioactive components of the roots ofPlatycodon grandiflorumand possesses multiple biological and pharmacological properties, such as antiviral, anti-inflammatory, and anti-cancer activities. However, whether it affects platelet function remains unclear. This study aims to evaluate the role of PD in platelet function and thrombus formation.MethodsPlatelets were treated with PD followed by measuring platelet aggregation, activation, spreading, clot retraction, expression of glycoprotein receptors. Moreover, mice platelets were treated with PD and infused into wild-type mice for analysis of in vivo hemostasis and arterial thrombosis.ResultsPlatycodin D treatment significantly inhibited platelet aggregation in response to collagen, ADP, arachidonic acid and epinephrine, reduced platelet P-selectin expression, integrin αIIbβ3activation, spreading on fibrinogen as well as clot retraction, accompanied with decreased phosphorylation of Syk and PLCγ2 in collagen-related peptide or thrombin-stimulated platelets. Moreover, PD-treated mice platelets presented significantly impaired in vivo hemostasis and arterial thrombus formation. Interestingly, PD induced internalization of glycoprotein receptors αIIbβ3, GPIbα and GPVI. However, GM6001, cytochalasin D, BAPTA-AM and wortmannin did not prevent PD-induced internalization of receptors.ConclusionsOur study demonstrates that PD inhibits platelet aggregation, activation and impairs hemostasis and arterial thrombosis, suggesting it might be a potent anti-thrombotic drug.
登录
查看更多内容
活性氧调节血小板活化和血栓形成。
影响因子：
11.4
作者：
Qiao J;Arthur JF;Gardiner EE;Andrews RK;Zeng L;Xu K
通讯作者：
Xu K
影响因子：
--
作者：
Nyakudya E;Jeong JH;Lee NK;Jeong YS
通讯作者：
Jeong YS
DOI：
10.1111/jth.13302
发表时间：
2016-05
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Bye AP;Unsworth AJ;Gibbins JM
通讯作者：
Gibbins JM
影响因子：
2.7
作者：
Lee, Eun Jeong;Kang, Minseok;Kim, Yeong Shik
通讯作者：
Kim, Yeong Shik
DOI：
10.1083/jcb.200703185
发表时间：
2007-11-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Flevaris P;Stojanovic A;Gong H;Chishti A;Welch E;Du X
通讯作者：
Du X