海藻被认为是功能性食品的有希望的候选者,并有助于预防血栓形成和相关的心血管疾病。Codium脆性(Suringer)Hariot传统上被用作烹饪成分,它具有一系列的生物活性,包括抑制血小板功能。然而,这种抑制作用的机制尚不清楚。本研究的目的是研究C.脆性C.对血小板功能的抑制作用。脆性梭菌对激动剂激活的血小板聚集的抗血小板活性,颗粒分泌,钙动员,血小板扩散,并评估凝块回缩。c-Src的磷酸化,Syk,还在凝血酶和CRP刺激的血小板中研究了PLCγ2和涉及αIIbβ3整合素外部信号通路的几种蛋白质。在体内使用氯化铁诱导的动脉血栓形成在小鼠中研究了抗血栓形成作用。使用横切尾部出血时间来评估脆性梭菌是否抑制原发性止血。通过GC-MS分析确定了C.脆性乙醇提取物的主要成分和含量。C.脆性显著受损激动剂诱导的血小板聚集颗粒分泌,钙动员,血小板扩散,和凝块收缩。生化分析表明,C.frageral抑制了激动剂诱导的c-Src活化,Syk,和PLCγ2,以及PI3K的磷酸化,AKT,和丝裂原活化蛋白激酶(MAPK)。脆性梭状芽胞杆菌的抑制作用是由于在细胞活化过程中抑制了血小板αIIbβ3整合素的信号转导。口服脆性梭菌可有效阻断FeCl3诱导的体内动脉血栓形成,而不会延长出血时间。GC-MS分析表明,植物醇是主要成分,异构体的总含量为160.8mg/kg。我们的结果表明,脆性梭状芽胞杆菌不仅抑制了αIIbβ3整合素的由内而外的信号传导,而且还抑制了由外而内的信号传递。因此,C.脆性C.可能是有效的抗血小板治疗候选物。
Seaweeds are thought to be promising candidates for functional foods and to help prevent thrombotic and related cardiovascular diseases. Codium fragile (Suringer) Hariot has been traditionally used as a culinary ingredient, and it possesses a range of biological activities, including the inhibition of platelet function. However, the mechanism of this inhibition is unclear. The aim of this study was to examine the inhibitory effect of C. fragile in platelet function. The antiplatelet activity of C. fragile on agonist-activated platelet aggregation, granule secretion, calcium mobilization, platelet spreading, and clot retraction was assessed. The phosphorylation of c-Src, Syk, PLCγ2, and several proteins involving in the αIIbβ3 integrin outside-in signaling pathway were also studied in thrombin and CRP-stimulated platelets. The antithrombotic effect was investigated in mice using ferric chloride-induced arterial thrombus formation in vivo. Transection tail bleeding time was used to evaluate whether C. fragile inhibited primary hemostasis. The main components and contents of C. fragile ethanol extract were confirmed by GC-MS analysis. C. fragile significantly impaired agonist-induced platelet aggregation granule secretion, calcium mobilization, platelet spreading, and clot retraction. Biochemical analysis revealed that C. fragile inhibited the agonist-induced activation of c-Src, Syk, and PLCγ2, as well as the phosphorylation of PI3K, AKT, and mitogen-activated protein kinases (MAPKs). The inhibitory effect of C. fragile resulted from an inhibition of platelet αIIbβ3 integrin outside-in signal transduction during cell activation. Oral administration of C. fragile efficiently blocked FeCl3-induced arterial thrombus formation in vivo without prolonging bleeding time. GC-MS analysis revealed that phytol was the main constituent and the total content of isomers was 160.8 mg/kg. Our results demonstrated that C. fragile suppresses not only the inside-out signaling of αIIbβ3 integrin but also outside-in signal transmission. Therefore, C. fragile could be an effective antiplatelet therapeutic candidate.