Antihypertensive Effects of Continuous Oral Administration of Nattokinase and Its Fragments in Spontaneously Hypertensive Rats

Abstract

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 3.4.15.1), 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.

Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease

“…Unlike common fibrinolytic proteases, such as t-PA and uPA, which can produce various side effects such as bleeding, NK exhibits little to no side effects. Studies also indicate that an oral administration of NK can be absorbed by the intestinal tract [3,4]. NK exhibits strong fibrinolytic activity after intraduodenal absorption.…”

Mechanisms of Nattokinase in protection of cerebral ischemia

“…Nattokinase (NK) was a serine proteinase produced by Bacillus subtilis (natto), that was isolated from natto (Sumi et al, 1987) that could dissolve thrombus and fibrin and it was originally discovered in natto (fermented soybean) and named by Japanese scholar H. Sum (Fujita et al, 1993(Fujita et al, , 1995. Compared with traditional anti-thrombotic drugs, NK is characterized by high safety, low cost, simple production process, oral availability and long in vivo half-life period, so it is expected to become a new generation thrombolytic drug (Fujita et al, 2011). At present, the studies on NK are mainly focused on the selection of high-yield strains and the optimization of fermentation parameters.…”

Nattokinase: production and application

“…When intact NK (having protease activity) is administered, blood pressure may decrease through the reduction of blood viscosity by cleaving plasma fibrinogen. On the other hand, the fragments obtained from NK suppress hypertension via downregulation of plasma angiotensin II level (Fujita et al 2011).…”