DOI QR코드

DOI QR Code

Evaluation of Nattokinase for Antithrombotic Effect and Pharmacological Efficacy by a Biological Test and Clinical Trial

동물 및 인체시험을 통한 Nattokinase의 항응고 작용 및 섬유소 용해능 평가

  • Received : 2011.07.21
  • Accepted : 2011.10.21
  • Published : 2011.10.31

Abstract

Bacillus subtilis natto producing high level of a fibrinolytic enzyme was selected and Ultra Nattokinase$^{(R)}$ was manufactured by fermentation and purification. It was performed the evaluation of the antithrombotic effect of Ultra Nattokinase$^{(R)}$ (20,000 FU/g) with rat blood plasma. The maximum aggregation (inhibition ratio) was 71% (0%), 69% (2.8%), 62% (12.7%), 16% (77.5%) and 9% (87.3%), respectively, in the order of 0, 5, 10, 50 and 100 mg/mL of Ultra Nattokinase$^{(R)}$ solutions. Ultra Nattokinase$^{(R)}$ had antithrombotic effect, which was associated with the suppression of collagen-induced platelet aggregation. Ultra Nattokinase$^{(R)}$ in the topic of the FDP (fibrinogen degradation products) in blood coagulation tests showed a significant increasing trend. And based on the daily record of meal 39 people of ITT (what ?) group consisted with 19 people of NP (what ?) group and 20 people of PN (what ?) group except four people, two people who took vitamin K affecting the experiment and two people who took alcohol, finding to be taken Ultra Nattokinase$^{(R)}$ showed an increase in the FDP value after four weeks. In addition, FDP value of 41 people of ITT group except two people having metabolic syndrome was increased by Ultra Nattokinase$^{(R)}$.

Keywords

References

  1. Fujita, M., K. Nomura, K. Hong, Y. Ito, A. Asada, and S. Nishimuro (1993) Purification and characterization of a strong fibrinolytic enzyme (nattokinase) in the vegetable cheese natto, a popular soybean fermented food in Japan. Biochem. Biophys. Res. Commun. 197: 1340-1347. https://doi.org/10.1006/bbrc.1993.2624
  2. Al Dieri R., S. Alban, S. Béguin, and H. C. Hemker (2004) Thrombin generation for the control of heparin treatment, comparison with the activated partial thromboplastin time. J. Thromb. Haemost. 2: 1395-1401. https://doi.org/10.1111/j.1538-7836.2004.00798.x
  3. Chang, Y. Y., J. S. Liu, S. L. Lai, H. S. Wu, and M. Y. Lan (2008) Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern. Med. 47: 467-469. https://doi.org/10.2169/internalmedicine.47.0620
  4. Omura, K., M. Hitosugi, X. Zhu, M. Ikeda, H. Maeda, and S. Tokudome (2005) A newly derived protein from Bacillus subtilis natto with both antithrombotic and fibrinolytic effects. J. Pharmacol. Sci. 99: 247-251. https://doi.org/10.1254/jphs.FP0050408
  5. Omura, K., M. Hitosugi, K. Kaketani, X. Zhu, H. Maeda, and S. Tokudome (2004) Fibrinolytic and anti-thrombotic effect of NKCP, the protein layer from Bacillus subtilis natto. Biofactors 22: 185-187. https://doi.org/10.1002/biof.5520220138
  6. Maat, M. P., A. C. de Bart, B. C. Hennis, P. Meijer, A. C. Havelaar, P. G. Mulder, and C. Kluft (1996) Interindividual and intraindividual variability in plasma fibrinogen, TPA antigen, PAI activity, and CRP in healthy, young volunteers and patients with angina pectoris. Arterioscler. Thromb. Vasc. Biol. 16: 1156-1162. https://doi.org/10.1161/01.ATV.16.9.1156
  7. Yamamoto, K., K. Takeshita, T. Kojima, J. Takamatsu, and H. Saito (2005) Aging and plasminogen activator inhibitor-1 (PAI-1) regulation: implication in the pathogenesis of thrombotic disorders in the elderly. Cardiovasc. Res. 66: 276-285. https://doi.org/10.1016/j.cardiores.2004.11.013
  8. Borawski, J. and M. Myśliwiec (2001) Plasma fibrinogen level is an important determinant of prolonged euglobulin clot lysis time in hemodialysis patients. Clin. Appl. Thromb. Hemost. 7: 296-299. https://doi.org/10.1177/107602960100700408
  9. Kowalski, E., M. Kopec, and Niewiarowski (1959) An evaluation of the euglobulin method for the determination of fibrinolysis. J. Clin. Pathol. 12: 215-218. https://doi.org/10.1136/jcp.12.3.215
  10. Sumi, H., H. Hamada, K. Nakanishi, and H. Hiratani (1990) Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematologica 84: 139-143. https://doi.org/10.1159/000205051
  11. Sasaki, K., S. Moriyama, Y. Tanaka, H. Sumi, N. Toki, and K. C. Robbins (1985) The transport of 125I-labeled human high molecular weight urokinase across the intestinal tract in a dog model with stimulation of synthesis and/or release of plasminogen activators. Blood 66: 69-75.
  12. Hirofumi O., T. Iwakoshi, M. Niwa, Y. Kida, T. Tanaka, R. Kitamura, S. Maezawa, and T. Kobayashi (1996) Coagulation and fibrinolysis study after local thrombolysis of a cerebral artery with urokinase. Neurol. Med. Chir. (Tokyo) 36: 300-304. https://doi.org/10.2176/nmc.36.300
  13. Yoo, C. K., W. S. Seo, C. S. Lee, and S. M. Kang (1998) Purification and characterization of fibrinolytic enzyme excreted by Bacillus subtilis K-54 isolated from Chung Guk Jang. Korean J. Appl. Microbiol. Biotechnol. 26: 507-514.
  14. Astrup, T. and S. Mullertz (1952) The fibrin plate method for estimating fibrinolytic activity. Archs. Biochem. Biophys. 40: 346-347. https://doi.org/10.1016/0003-9861(52)90121-5
  15. Anson, M. L. (1939) The estimation of pepsin, trypsin, papain and cathepsin with hemoglobin. J. Gen. Physiol. 22: 78-89.
  16. Kimura, S., M. T. Chiang, and H. Fujimoto (1990) Effects of eicosapentanoic acid an soybean protein on plasma cholesterol, blood pressure and platelet aggregation in stroke prone spontaneously hypertensive rats. Monogr. Atheroscler. 16: 26-35.

Cited by

  1. The Evaluation of Antithrombotic and Fibrinolytic Activities of Nattokinase from Bacillus subtilis Natto vol.27, pp.6, 2012, https://doi.org/10.7841/ksbbj.2012.27.6.375