College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, China.
Arch Pharm Res. 2015 Aug;38(8):1530-40. doi: 10.1007/s12272-014-0518-y. Epub 2014 Dec 5.
Fungi fibrinolytic compound 1 (FGFC1) is a novel marine natural product as a low-weight fibrinolytic pyranoindole molecule, whose thrombolytic effects were evaluated on FITC-fibrin (Fluorescein isothiocyanate, FITC) degradation methods in vitro and on acute pulmonary thromboembolism animal model in vivo. We determined the FGFC1 induced thrombolysis that stems from its fibrin(ogen)olytic activities as measured by fibrin(ogen) degradation products (FDPs) experiment, acute pulmonary thromboembolism animal model experiment, and euglobulin lysis assay. In vitro, measurement of FITC-fibrin degradation revealed that fibrin hydrolysis occurred in a concentration-dependent manner of FGFC1 from 5 to 25 μ mol/L. In vivo test of a classical acute pulmonary thromboembolism model in rat showed that when the injected dose was 5 mg/kg or above, FGFC1 was effective in dissolution of extrinsic FITC-fibrin induced blood clots. Euglobulin lysis time (ELT) in FGFC1-treated rats was shortened 30 s compared with rats in the positive control group, which were injected with clopidogrel sulfate and single-chain urokinase-type plasminogen activator. As compared to the control, FGFC1 (5-25 mg/kg) did not significantly alter the formation of fibrinogen and FDPs in vivo. Our research indicates that FGFC1 presents pharmacodynamic action in both the thrombolysis and the hemolytic procedure, which can be characterized by fibrinogenolysis in blood and FDPs in plasma. In vivo, increasing fibrinolytic doses of FGFC1 from 5 to 25 mg/kg did not induce fibrinogenolysis when compared with control group, this result corresponds to that FGFC1 did not induce the increasing of FDPs (compared with the saline-treated control). It indicates that the FGFC1 may act as a novel thrombolytic agent and represent an effective approach to the treatment of thrombus without significant risk of hemorrhagic activity.
真菌纤溶化合物 1（FGFC1）是一种新型海洋天然产物，作为一种低分子量的纤溶吡喃吲哚分子，其溶栓作用在 FITC-纤维蛋白（荧光素异硫氰酸酯，FITC）体外降解方法和体内急性肺血栓栓塞动物模型中进行了评估。我们通过纤维蛋白（原）降解产物（FDPs）实验、急性肺血栓栓塞动物模型实验和优球蛋白溶解试验来确定 FGFC1 诱导的溶栓作用，该作用源于其纤维蛋白（原）水解活性。在体外，通过 FITC-纤维蛋白降解的测量表明，FGFC1 在 5 至 25 μmol/L 的浓度范围内以浓度依赖性方式发生纤维蛋白水解。在大鼠经典急性肺血栓栓塞模型的体内试验中，当注射剂量为 5mg/kg 或更高时，FGFC1 可有效溶解外源性 FITC-纤维蛋白诱导的血栓。与阳性对照组（注射硫酸氯吡格雷和单链尿激酶型纤溶酶原激活剂）相比，FGFC1 治疗大鼠的优球蛋白溶解时间（ELT）缩短了 30s。与对照组相比，FGFC1（5-25mg/kg）在体内并未显著改变纤维蛋白原和 FDPs 的形成。我们的研究表明，FGFC1 在溶栓和溶血过程中均表现出药效作用，其特征在于血液中的纤维蛋白原水解和血浆中的 FDPs。在体内，FGFC1 的纤维蛋白溶解剂量从 5 至 25mg/kg 增加时，与对照组相比并未引起纤维蛋白原水解，这一结果与 FGFC1 未引起 FDPs 增加（与生理盐水处理的对照组相比）的结果相对应。这表明 FGFC1 可能作为一种新型溶栓剂，代表了一种治疗血栓的有效方法，而不会显著增加出血活性的风险。
