Thrombolytic Effects in vivo of Nattokinase in a Carrageenan-Induced Rat Model of Thrombosis

Abstract

Background/Aims: Nattokinase is a serine protease produced by Bacillus subtilis during the fermentation of the soybean product natto. The fibrinolytic activity and thrombolytic effects of nattokinase have been observed in vitro, but the effect in vivo has still to be researched. The objective of this study was to demonstrate the activity of nattokinase in vivo. Methods: To establish a rat model of thrombosis, κ-carrageenan was injected subcutaneously into the toes of Sprague-Dawley (SD) rats. Histological examination confirmed thrombosis. The rats were then treated with varying doses of nattokinase and the resulting thrombolysis was histologically assessed. ELISA was used to determine the levels of the fibrin/fibrinogen degradation products (FDPs) and D-dimer, which are sensitive indices of fibrinolytic activity. Vermis kinase, a known thrombolytic agent, was used as a positive control. Results: Biopsy results revealed partial thrombolysis in the tail vessels of the rats treated with nattokinase or vermis kinase. FDP and D-dimer levels were higher in rats treated with high-dose nattokinase than in those treated with saline. No difference in FDP or D-dimer levels was observed between rats treated with high-dose nattokinase and those treated with vermis kinase. Conclusions: Both the histological and physiological evidence from this study indicate that nattokinase exerts thrombolytic effects in vivo.

Global deregulation of ginseng products may be a safety hazard to warfarin takers: solid evidence of ginseng-warfarin interaction

“…Here we used the well-established K-carrageenan-induced rat tail thrombosis model 22, 23 to further investigate whether GS intervenes the warfarin’s anti-coagulation effect. As shown in Fig.…”

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

“…NK was reported to have an effect on both oxidative injury-mediated arterial thrombosis [12,13] and inflammation-induced venal thrombosis [14]. When ferric chloride (FeCl 3 ) was administered to the injured arteries, it resulted in oxidative thrombosis and platelet adhesion.…”

“…Unlike aspirin, which often triggers bleeding or gastric ulcers, NK improves blood flow without any adverse effects. κ-Carrageenan-induced inflammatory thrombi formation in rat tails was used to examine the effect of NK [14]. Twelve hours after gavage administration of NK, higher levels of fibrin degradation product (FDP) fragments and d -dimers were detected in blood samples.…”

Nattokinase: production and application

“…Among these enzymes, NK is assumed an interesting one. This considerable interest is due to the direct fibrinolytic activity of this enzyme, both in vitro and in vivo (Fujita et al 1995a;Kamiya et al 2010;Xu et al 2014). It not only degrades fibrin directly but also increases the release of tissue plasminogen activator from cells to degrade fibrin (Yatagai et al 2008).…”