Antimicrobial Peptide Cathelicidin-BF Inhibits Platelet Aggregation by Blocking Protease-Activated Receptor 4

  • Guofang Shu
  • Yahui Chen
  • Tongdan Liu
  • Shenhong Ren
  • Yi KongEmail author


Cathelicidin-BF (BF-30), a peptide isolated from the snake venom of Bungarus fasciatus, exhibits multiple biological functions, including antimicrobial, anticancer and anti-inflammatory. However, the effect of BF-30 on platelet and thrombus formation was reported rarely. In this study, we investigated the antiplatelet and antithrombotic effects of BF-30 and its underlying mechanism. Our results showed that BF-30 potently inhibited thrombin-induced platelet aggregation, and further specifically blocked protease-activated receptor 4 (PAR4). It also reduced P-selectin expression, AktSer473 phosphorylation and platelet spreading on fibrinogen. Furthermore, BF-30 exhibited potent inhibitory activity on thrombus formation in vivo: it decreased death of mice with acute pulmonary thrombosis and attenuated thrombosis weight in arterio-venous shunt model. Additionally, a tail cutting bleeding time assay revealed that BF-30 did not prolong bleeding time in mice at efficient dosage. Taken together, BF-30 is a PAR4 antagonist, and inhibits thrombus formation without obvious bleeding risk in vivo. We believe that this study may provide a source for the development of PAR4 antagonist for the treatment of thrombotic disorders.


Cathelicidin-BF Protease-activated receptor 4 Antagonist Platelet aggregation Antithrombosis 



This study was supported by the Chinese National Natural Science Foundation (81273375) and the Priority Academic Program Development of Jiangsu Higher Education Institutions.

Compliance with Ethical Standards

Conflict of interest

Guofang Shu, Yahui Chen, Tongdan Liu, Shenhong Ren and Yi Kong declares that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Informed Consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Guofang Shu
    • 1
  • Yahui Chen
    • 2
  • Tongdan Liu
    • 2
  • Shenhong Ren
    • 2
  • Yi Kong
    • 2
    Email author
  1. 1.Center of Clinical Laboratory Medicine of Zhongda HospitalSoutheast UniversityNanjingPeople’s Republic of China
  2. 2.School of Life Science & TechnologyChina Pharmaceutical UniversityNanjingPeople’s Republic of China

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