Antihypertensive effects of continuous oral administration of nattokinase and its fragments in spontaneously hypertensive rats

Biol Pharm Bull. 2011;34(11):1696-701. doi: 10.1248/bpb.34.1696.


To determine whether the antihypertensive effect of nattokinase is associated with the protease activity of this enzyme, we compared nattokinase with the fragments derived from nattokinase, which possessed no protease activity, in terms of the effect on hypertension in spontaneously hypertensive rats (SHR). In the continuous oral administration test, the groups were given a basic diet alone (control), the basic diet containing nattokinase (0.2, 2.6 mg/g diet) or the basic diet containing the fragments derived from nattokinase (0.2, 0.6 mg/g diet). The group fed the basic diet containing high-dosage nattokinase (2.6 mg/g diet) showed significant reductions in systolic blood pressure (SBP), diastolic blood pressure (DBP) and plasma fibrinogen level, compared with control group and no influence on activities of renin and angiotensin-converting enzyme (ACE, EC, and plasma angiotensin II level in the renin-angiotensin system. The treatment of the basic diet containing high-dosage fragments (0.6 mg/g diet) significantly decreased SBP, DBP and plasma angiotensin II level in plasma but the treatment did not influence on plasma fibrinogen level. These results suggest that nattokinase and its fragments are different from each other in the mechanism to reduce hypertension. Nattokinase, retained its protease activity after absorbance across the intestines, may decrease blood pressure through cleavage of fibrinogen in plasma. The fragments, which absorbed as nattokinase-degradation products, prevents the elevation of plasma angiotensin II level to suppress hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Angiotensin II / blood
  • Animals
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects*
  • Fibrinogen / metabolism
  • Glycine max / chemistry*
  • Hypertension / blood
  • Hypertension / drug therapy*
  • Intestinal Absorption
  • Male
  • Peptide Hydrolases / blood
  • Phytotherapy*
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Rats
  • Rats, Inbred SHR
  • Soy Foods*
  • Subtilisins / administration & dosage
  • Subtilisins / pharmacology
  • Subtilisins / therapeutic use*


  • Antihypertensive Agents
  • Plant Extracts
  • Angiotensin II
  • Fibrinogen
  • Peptide Hydrolases
  • Subtilisins
  • nattokinase