Department of Pharmacology, Tongji Medical College of Huazhong University of Science & Technology, 13 Hangkong Road, Wuhan 430000, China.
Thromb Res. 2013 Aug;132(2):202-10. doi: 10.1016/j.thromres.2013.05.018. Epub 2013 Jun 14.
Neferine, a kind of isoquinoline alkaloid, extracted from the seed embryo of Nelumbo nucifera Gaertn, has long been recognized in traditional medicine as a medicinal plant with various usages. Neferine has many biological activities, including anti-hypertensive, anti-arrhythmic, negative inotropic effect and relaxation on vascular smooth muscle. Although previous studies have reported its antithrombotic effect, the mechanisms by which it exerts antithrombotic effect have not been thoroughly studied.
Washed mice platelets and mice platelet-rich-plasma (PRP) were used to investigate the effects of neferine on platelet aggregation, secretion induced by various agonists and dissociation of agonist-formed platelet aggregates. Bioflux plates coated with collagen were used to investigate the effect of neferine on platelet adhesion and thrombosis in vitro. With collagen-epinephrine-induced acute pulmonary thrombus formation mouse model, the effect of neferine on thrombosis in vivo was also examined.
Neferine, significantly and dose-dependently, inhibited collagen-, thrombin-, U46619-induced platelet aggregation in mice washed platelets, or ADP-induced platelet aggregation in PRP. Neferine treatment decreased platelet dense granule secretion initiated by collagen, thrombin and U46619. Also, Neferine dramatically and dose-dependently promoted the dissociation of platelet aggregates pre-formed by various agonists including collagen, thrombin, U46619 or ADP. Neferine can significantly reduce the area of mice platelets adhesion to the collagen and inhibit thrombosis in vitro. In collagen-epinephrine-induced acute pulmonary thrombus mouse model, neferine, at 6 mg/kg, significantly attenuated thrombus formation.
Neferine remarkably prevents thrombus formation by inhibiting platelet activation, adhesion and aggregation, as well as promoting disassembly of pre-formed platelet aggregates. The inhibitory effects of neferine on platelet activation might be relevant in cases involving aberrant platelet activation where neferine could be used as an anti-platelet and antithrombotic agent.
荷叶碱，一种从莲的种子胚胎中提取的异喹啉生物碱，在传统医学中一直被认为是一种具有多种用途的药用植物。荷叶碱具有多种生物活性，包括降压、抗心律失常、负性肌力作用和血管平滑肌松弛作用。虽然以前的研究已经报道了它的抗血栓作用，但它发挥抗血栓作用的机制尚未得到彻底研究。
使用洗涤后的小鼠血小板和富含血小板的血浆（PRP）来研究荷叶碱对血小板聚集、各种激动剂诱导的分泌以及激动剂形成的血小板聚集物解聚的影响。生物通量板用胶原蛋白包被，用于研究荷叶碱对体外血小板黏附与血栓形成的影响。使用胶原蛋白-肾上腺素诱导的急性肺血栓形成小鼠模型，还研究了荷叶碱对体内血栓形成的影响。
荷叶碱显著且剂量依赖性地抑制了胶原、凝血酶、U46619 诱导的小鼠洗涤血小板聚集或 ADP 诱导的 PRP 血小板聚集。荷叶碱处理减少了胶原、凝血酶和 U46619 引发的血小板致密颗粒分泌。此外，荷叶碱显著且剂量依赖性地促进了各种激动剂（包括胶原、凝血酶、U46619 或 ADP）预形成的血小板聚集物的解聚。荷叶碱能显著减少小鼠血小板在胶原蛋白上的黏附面积并抑制体外血栓形成。在胶原蛋白-肾上腺素诱导的急性肺血栓形成小鼠模型中，荷叶碱（6mg/kg）显著减轻血栓形成。
荷叶碱通过抑制血小板激活、黏附和聚集以及促进已形成的血小板聚集物的解聚，显著防止血栓形成。荷叶碱对血小板激活的抑制作用可能与异常血小板激活有关，在这种情况下，荷叶碱可作为抗血小板和抗血栓药物。
