title: Effects of a novel marine natural product: pyrano indolone alkaloid fibrinolytic compound on thrombolysis and hemorrhagic activities in vitro and in vivo.
abstract: 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.
authors.affiliation: College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yan
authors.forename: Wenhui
authors.initials: W
authors.lastname: Wu
authors.forename: Tongwei
authors.initials: T
authors.lastname: Su
authors.forename: Jiajie
authors.initials: J
authors.lastname: Chen
authors.forename: Quangang
authors.initials: Q
authors.lastname: Zhu
authors.forename: Chaoyan
authors.initials: C
authors.lastname: Zhang
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Bao
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification / Q000627:therapeutic use*; D000818:Animals; D001688:Biological Products / Q000302:isolation & purification / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005343:Fibrinolytic Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D006470:Hemorrhage / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013191:Stachybotrys; D013927:Thrombosis / Q000188:drug therapy / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000470:Alkaloids; D001688:Biological Products; D005343:Fibrinolytic Agents