Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat

Biol Pharm Bull. 1995 Oct;18(10):1387-91. doi: 10.1248/bpb.18.1387.


Nattokinase is a new fibrinolytic enzyme which cleaves directly cross-linked fibrin in vitro. In this study, we investigated the thrombolytic effect of nattokinase on a thrombus in the common carotid artery of rat in which the endothelial cells of the vessel wall were injured by acetic acid. When a section of occluded vessel was stained for CD61 antigen by immunofluorescence utilizing a monoclonal antibody, the antigen was localized around the surface of the occluded blood vessels. This result suggests that the occlusive thrombosis was caused by platelet aggregation. In addition, thrombolysis with urokinase (UK; 50000 IU/kg, i.v.) or tissue plasminogen activator (tPA; 13300 IU/kg, i.v.) in our model was observed to restore the blood flow over a 60 min monitoring period. The results indicate that our chemically induced model is useful for screening and evaluating a thrombolytic agent. We evaluated the thrombolytic activity of nattokinase using this model and compared it with fibrino(geno)lytic enzyme, plasmin or elastase. On a molar basis, the recovery of the arterial blood flow with nattokinase, plasmin and elastase were 62.0 +/- 5.3%, 15.8 +/- 0.7% and 0%, respectively. The results indicate that the thrombolytic activity of nattokinase is stronger than that of plasmin or elastase in vivo.

MeSH terms

  • Animals
  • Carotid Artery Thrombosis / chemically induced
  • Carotid Artery Thrombosis / drug therapy*
  • Carotid Artery Thrombosis / physiopathology
  • Carotid Artery, Common
  • Drug Evaluation, Preclinical
  • Fibrinolysin / therapeutic use
  • Fibrinolytic Agents / pharmacology*
  • Fluorescent Antibody Technique, Direct
  • Male
  • Pancreatic Elastase / therapeutic use
  • Rats
  • Rats, Wistar
  • Regional Blood Flow / drug effects
  • Regional Blood Flow / physiology
  • Serine Endopeptidases / pharmacology*
  • Subtilisins*
  • Tissue Plasminogen Activator / therapeutic use
  • Urokinase-Type Plasminogen Activator / therapeutic use


  • Fibrinolytic Agents
  • Serine Endopeptidases
  • Subtilisins
  • Pancreatic Elastase
  • Tissue Plasminogen Activator
  • Fibrinolysin
  • Urokinase-Type Plasminogen Activator
  • nattokinase