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Effects of a novel marine natural product: pyrano indolone alkaloid fibrinolytic compound on thrombolysis and hemorrhagic activities in vitro and in vivo

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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.

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Acknowledgments

This work received financial support from National High Technology Research and Development Program of China (No.2011AA09070109), National Natural Science Foundation of China (No. 81341082), Supported by special funding for the development of science and technology of Shanghai Ocean University and Marine Pharmaceutical-food Science Interdis-ciplinary Project of Shanghai Ocean University.

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Authors and Affiliations

  1. College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, China

    Ting Yan, Tongwei Su, Jiajie Chen, Chaoyan Zhang & Bin Bao

  2. Shanghai Engineering Research Center of Aquatic Product Processing & Preservation, Institutes of Marine Science, Shanghai Ocean University, Shanghai, 201306, China

    Wenhui Wu & Bin Bao

  3. Institutes of Marine Science, Shanghai Ocean University, Shanghai, 201306, China

    Wenhui Wu & Xiaoyu Wang

  4. Yueyang hospital integrated traditional Chinese and western medicine, Shanghai university of traditional Chinese medicine, Shanghai, 200437, China

    Quangang Zhu

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  1. Ting Yan
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Correspondence to Bin Bao.

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Ting Yan and Wenhui Wu authors contributed equally to this work.

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Yan, T., Wu, W., Su, T. et al. Effects of a novel marine natural product: pyrano indolone alkaloid fibrinolytic compound on thrombolysis and hemorrhagic activities in vitro and in vivo. Arch. Pharm. Res. 38, 1530–1540 (2015). https://doi.org/10.1007/s12272-014-0518-y

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