The inhibitory effect of tachyplesin I on thrombosis and its mechanisms

Chem Biol Drug Des. 2019 Sep;94(3):1672-1679. doi: 10.1111/cbdd.13570. Epub 2019 Jun 12.

Abstract

Thrombotic diseases are major cause of cardiovascular diseases. This study was designed to investigate the effect of tachyplesin I on platelet aggregation and thrombosis. Platelet aggregation was analysed with a whole blood aggregometer. The mice were employed to investigate the effect of tachyplesin I on thrombosis in vivo. Tachyplesin I inhibited thrombin-induced platelet aggregation in a dose-dependent manner. Furthermore, tachyplesin I significantly reduced thrombosis in carrageenan-induced tail thrombosis model by intraperitoneal injection (0.1, 0.2 or 0.4 mg/kg) or intragastric administration (15, 30 or 60 mg/kg). Tachyplesin I also prolonged the bleeding time (BT) and clotting time (CT). The results revealed that tachyplesin I inhibited platelet aggregation and thrombosis by interfering the PI3K/AKT pathway. Tachyplesin I did not show significantly toxicity to mice under 300 mg/kg via intravenous injection. The results show that tachyplesin I inhibits thrombosis and has low toxicity. It is suggested that tachyplesin I has the potential to develop a new anti-thrombotic drug.

Keywords: PI3K/Akt; anti-thrombosis; platelet aggregation; tachyplesin I.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / administration & dosage
  • Antimicrobial Cationic Peptides / chemistry*
  • Bleeding Time
  • Blood Platelets / metabolism
  • DNA-Binding Proteins / administration & dosage
  • DNA-Binding Proteins / chemistry*
  • Dose-Response Relationship, Drug
  • Drug Development
  • Humans
  • Mice
  • Models, Animal
  • Peptides, Cyclic / administration & dosage
  • Peptides, Cyclic / chemistry*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / chemistry*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Thrombin / metabolism
  • Thrombosis / drug therapy*

Substances

  • Antimicrobial Cationic Peptides
  • DNA-Binding Proteins
  • Peptides, Cyclic
  • Platelet Aggregation Inhibitors
  • tachyplesin peptide, Tachypleus tridentatus
  • Proto-Oncogene Proteins c-akt
  • Thrombin