Dietary Supplementation of Fermented Soybean, Natto, Suppresses Intimal Thickening and Modulates the Lysis of Mural Thrombi After Endothelial Injury in Rat Femoral Artery

Life Sci. 2003 Jul 25;73(10):1289-98. doi: 10.1016/s0024-3205(03)00426-0.


We have previously demonstrated that natto-extracts containing nattokinase (NK) inactivates plasminogen activator inhibitor type 1 and then potentiates fibrinolytic activity. In the present study, we investigated the effects of dietary supplementation with natto-extracts on neointima formation and on thrombolysis at the site of endothelial injury. Endothelial damage in the rat femoral artery was induced by intravenous injection of rose bengal followed by focal irradiation by transluminal green light. Dietary natto-extracts supplementation containing NK of 50 or 100 CU/body was started 3 weeks before endothelial injury and then continued for another 3 weeks. Intimal thickening in animals given supplementation was significantly (P<0.01) suppressed compared with controls and the intima/media ratio in animals with 50 and 100 CU/body NK and control group was 0.09 +/- 0.03, 0.09 +/- 0.06 and 0.16 +/- 0.12, respectively. Although femoral arteries were reopened both in control animals and those treated with NK within 8 hours after endothelial injury, mural thrombi were histologically observed at the site of endothelial injury. In the control group, the center of vessel lumen was reopened and mural thrombi were attached on the surface of vessel walls. In contrast, in NK-treated groups, thrombi near the vessel wall showed lysis and most of them detached from the surface of vessel walls. In conclusion, dietary natto-extracts supplementation suppressed intimal thickening produced by endothelial injury in rat femoral artery. These effects may partially be attributable to NK, which showed enhanced thrombolysis near the vessel wall.

MeSH terms

  • Animals
  • Dietary Supplements
  • Disease Models, Animal
  • Femoral Artery / drug effects*
  • Femoral Artery / pathology
  • Fibrinolytic Agents / pharmacology*
  • Fibrinolytic Agents / therapeutic use
  • Male
  • Plant Extracts / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Soybeans*
  • Subtilisins / pharmacology*
  • Subtilisins / therapeutic use
  • Thrombolytic Therapy*
  • Thrombosis / diet therapy
  • Thrombosis / etiology
  • Thrombosis / pathology*
  • Tunica Intima / drug effects*
  • Tunica Intima / pathology
  • Tunica Intima / radiation effects


  • Fibrinolytic Agents
  • Plant Extracts
  • Subtilisins
  • nattokinase