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A brief analysis of nattokinase.
Thrombosis is an "uninvited guest" in the blood, which can block normal blood circulation and cause severe ischemia in distal organs, leading to a series of disabling consequences, and even death. In modern society, thromboembolic diseases are frequent and have become the second largest condition after cancer. One of the important reasons for thrombosis is the reduced function of the fibrinolytic system in the body, compared to traditional thrombolytic drugs such as urokinase (UK), streptokinase (SK), and tissue-type plasminogen activator (tPA).Nattokinasehas unique advantages and is expected to become a new approach for the prevention and treatment of thromboembolic diseases.
Physicochemical properties of nattokinase
Nattokinase (NK), produced by the fermentation of Bacillus subtilis natto, is a strongly fibrinolytic alkaline serine protease, appearing white or light yellow in solid form and soluble in water. Although it has been established that nattokinase is a single-chain polypeptide consisting of 275 amino acids, the relative molecular weight measured by different detection methods varies. Within the pH range of 6.0-12.0, nattokinase exhibits strong and stable thrombolytic ability, while its thrombolytic ability becomes extremely unstable at pH below 5.0. Under a 40°C environment, the activity of nattokinase remains unchanged after 30 minutes, but the enzyme activity gradually loses at temperatures above 50°C, and rapidly inactivates above 60°C. However, repeated freeze-thaw cycles have little effect on enzyme activity. Experiments have shown that when mixed with serum proteins, gastric mucin, and extracts from boiled wheat, rice, and broth, the stability of nattokinase significantly increases, and even under acidic conditions, the enzyme activity only partially disappears, proving the feasibility of oral administration of nattokinase for thrombolysis.
Mechanism of action of nattokinase
Martin et al. studied 200 substances with oral fibrinolytic effects and evaluated nattokinase as the most promising fibrinolytic protease discovered to date. The thrombolytic activity of nattokinase is four times that of plasmin, and its thrombolytic speed is 19 times that of urokinase. Nattokinase hydrolyzes fibrinogen to generate small peptides and amino acids for direct thrombolysis, and on the other hand, it stimulates the vascular endothelium by penetrating the intestinal wall to produce endogenous plasminogen activator, achieving a dual thrombolytic effect. Nattokinase can also convert plasminogen in the body into urokinase, thereby activating plasminogen to produce plasmin, increasing endogenous plasmin to dissolve blood clots. Another pathway for nattokinase to dissolve blood clots is by degrading and inactivating inhibitors of plasminogen activators.
In 1998, Dr. Xu Jianyang conducted experiments on rats using an 80% ethanol extract of freeze-dried powder containing nattokinase to perform blood pressure reduction experiments, confirming for the first timeNattokinasethat the extract has blood pressure-lowering effects. Further research by Murakami et al. confirmed that it is not nattokinase itself that has the blood pressure-lowering effect, but rather small peptide fragments produced from the cleavage of nattokinase protein after high-temperature treatment, which can control vascular contraction and relaxation by inhibiting angiotensin-converting enzyme, leading to a decrease in systolic and diastolic blood pressure.
Nattokinase can reduce lipid peroxidation levels through direct antioxidant effects, improve lipid metabolism, lower blood lipids, and simultaneously prevent the occurrence of atherosclerosis. An animal experiment confirmed that nattokinase significantly reduces total cholesterol, serum triglycerides, and LDL cholesterol levels. NK clears blood clots through thrombolytic action, slows down the process of plaque formation; regulates blood flow speed through blood pressure-lowering effects; and prevents lipid oxidation through lipid-lowering effects, thereby reversing atherosclerotic lesions and purifying the blood environment. In other words, the efficacy of NK in combating atherosclerosis and improving the blood environment is a comprehensive effect of anti-thrombosis, anti-coagulation, antioxidant, and lipid-lowering.
Wu Jiechen et al. reported in 2003 on the role of nattokinase in the prevention and treatment of osteoporosis and diabetes. Zhan Huiqin et al. reported in the Journal of Nanjing Medical University in 2010 that nattokinase has a partial improvement effect on the retina in animals with central retinal artery and vein occlusion. There are also reports that nattokinase can induce posterior vitreous detachment, thus it can be used for a new type of ocular vitreolysis.
References:
[1] Xia Pan, Pengyu Liang, Luyao Teng, Yuhao Ren, Jixian Peng, Weizhi Liu, Yan Yang. Study on molecular mechanisms of nattokinase in pharmacological action based on label-free liquid chromatography–tandem mass spectrometry. Food Science & Nutrition, 2019;00:1–9.
[2] Xie Xin, Yi Xiang. Research progress and development prospects of nattokinase. Shandong Food Fermentation, 2014.4(175):22-25.
Note: This article is for informational purposes only and is not intended as medical guidance.
Nattokinase, natto powder, Chuangyuan Yixin, Chuangyuan Yisheng, Chuangyuan Biotechnology
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