A Newly Derived Protein From Bacillus subtilis natto With Both Antithrombotic and Fibrinolytic Effects

Natto, steamed soybeans fermented by Bacillus subtilis natto, is a traditional Japanese food. We derived a purified protein layer, called NKCP as a trade mark, from B. subtilis natto fermentation. In the present study, we examined the fibrinolytic and antithrombotic effects of NKCP and identified it...

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Main Authors: Kazunobu Omura, Masahito Hitosugi, Xia Zhu, Masashi Ikeda, Hiroaki Maeda, Shogo Tokudome
Format: Article
Language:English
Published: Elsevier 2005-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319320961
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author Kazunobu Omura
Masahito Hitosugi
Xia Zhu
Masashi Ikeda
Hiroaki Maeda
Shogo Tokudome
author_facet Kazunobu Omura
Masahito Hitosugi
Xia Zhu
Masashi Ikeda
Hiroaki Maeda
Shogo Tokudome
author_sort Kazunobu Omura
collection DOAJ
description Natto, steamed soybeans fermented by Bacillus subtilis natto, is a traditional Japanese food. We derived a purified protein layer, called NKCP as a trade mark, from B. subtilis natto fermentation. In the present study, we examined the fibrinolytic and antithrombotic effects of NKCP and identified its active component to clarify the fibrinolytic effect of NKCP observed in preliminary clinical trials previously. The active component of NKCP was identified as a 34-kilodalton protein designated bacillopeptidase F. NKCP showed direct degradation of artificial blood clot in saline. The protease activity, accounting for the fibrinolytic effect of NKCP, was examined with a chromogenic substrate for plasmin. Dose-dependent prolongations of both prothrombin time and active partial thromboplastin time were observed in rats with intraduodenum administration of NKCP. Our in vitro and in vivo studies suggest that NKCP has both a fibrinolytic effect and an antithrombotic effect similar to heparin. Because NKCP is derived from food and has safety data demonstrated by previous animal experiments and preliminary clinical trials, NKCP is considered as safe for clinical use. Keywords:: bacillopeptidase F, antithrombosis, fibrinolysis, Natto, Bacillus subtilis natto
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spelling doaj.art-034fd2cf03dd47dfa1cdeefd996ef3db2022-12-22T03:18:48ZengElsevierJournal of Pharmacological Sciences1347-86132005-01-01993247251A Newly Derived Protein From Bacillus subtilis natto With Both Antithrombotic and Fibrinolytic EffectsKazunobu Omura0Masahito Hitosugi1Xia Zhu2Masashi Ikeda3Hiroaki Maeda4Shogo Tokudome5Department of Legal Medicine, Dokkyo University School of Medicine, 880 Kita-Kobayashi, Mibu, Tochigi 321-0293, Japan; Corresponding author. FAX: +81-282-86-7678 E-mail: omura@dokkyomed.ac.jpDepartment of Legal Medicine, Dokkyo University School of Medicine, 880 Kita-Kobayashi, Mibu, Tochigi 321-0293, JapanResearch and Development Division, Daiwa Pharmaceutical Company, Ltd., 1-16-19 Sangenjaya, Setagaya-ku, Tokyo 154-0024, JapanInstitute for Medical Science, Dokkyo University School of Medicine, 880 Kita-Kobayashi, Mibu, Tochigi 321-0293, JapanResearch and Development Division, Daiwa Pharmaceutical Company, Ltd., 1-16-19 Sangenjaya, Setagaya-ku, Tokyo 154-0024, JapanDepartment of Legal Medicine, Dokkyo University School of Medicine, 880 Kita-Kobayashi, Mibu, Tochigi 321-0293, JapanNatto, steamed soybeans fermented by Bacillus subtilis natto, is a traditional Japanese food. We derived a purified protein layer, called NKCP as a trade mark, from B. subtilis natto fermentation. In the present study, we examined the fibrinolytic and antithrombotic effects of NKCP and identified its active component to clarify the fibrinolytic effect of NKCP observed in preliminary clinical trials previously. The active component of NKCP was identified as a 34-kilodalton protein designated bacillopeptidase F. NKCP showed direct degradation of artificial blood clot in saline. The protease activity, accounting for the fibrinolytic effect of NKCP, was examined with a chromogenic substrate for plasmin. Dose-dependent prolongations of both prothrombin time and active partial thromboplastin time were observed in rats with intraduodenum administration of NKCP. Our in vitro and in vivo studies suggest that NKCP has both a fibrinolytic effect and an antithrombotic effect similar to heparin. Because NKCP is derived from food and has safety data demonstrated by previous animal experiments and preliminary clinical trials, NKCP is considered as safe for clinical use. Keywords:: bacillopeptidase F, antithrombosis, fibrinolysis, Natto, Bacillus subtilis nattohttp://www.sciencedirect.com/science/article/pii/S1347861319320961
spellingShingle Kazunobu Omura
Masahito Hitosugi
Xia Zhu
Masashi Ikeda
Hiroaki Maeda
Shogo Tokudome
A Newly Derived Protein From Bacillus subtilis natto With Both Antithrombotic and Fibrinolytic Effects
Journal of Pharmacological Sciences
title A Newly Derived Protein From Bacillus subtilis natto With Both Antithrombotic and Fibrinolytic Effects
title_full A Newly Derived Protein From Bacillus subtilis natto With Both Antithrombotic and Fibrinolytic Effects
title_fullStr A Newly Derived Protein From Bacillus subtilis natto With Both Antithrombotic and Fibrinolytic Effects
title_full_unstemmed A Newly Derived Protein From Bacillus subtilis natto With Both Antithrombotic and Fibrinolytic Effects
title_short A Newly Derived Protein From Bacillus subtilis natto With Both Antithrombotic and Fibrinolytic Effects
title_sort newly derived protein from bacillus subtilis natto with both antithrombotic and fibrinolytic effects
url http://www.sciencedirect.com/science/article/pii/S1347861319320961
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