Advance on Nattokinase Microbial Production and Physiological Function

YAO Mingjing; YANG Yang; FAN Jing; ZHAO Xiangying; REN Likun; BIAN Xin; XING Tonglin; ZHU Pengyu; SUN Zhihui; ZHANG Na

doi:10.13386/j.issn1002-0306.2021070016

Volume 43 Issue 14

Jul. 2022

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Science and Technology of Food Industry > 2022 > 43(14): 435-444. > DOI: 10.13386/j.issn1002-0306.2021070016

YAO Mingjing, YANG Yang, FAN Jing, et al. Advance on Nattokinase Microbial Production and Physiological Function[J]. Science and Technology of Food Industry, 2022, 43(14): 435−444. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2021070016.

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Advance on Nattokinase Microbial Production and Physiological Function

1.
Key Laboratory of Food Science and Engineering of Heilongjiang Province, College of Food Science and Engineering, Harbin University of Commerce, Harbin 150076, China
2.
Shandong Provincial Key Laboratory of Food and Fermentation Engineering, Shandong Food Ferment Industry Research & Design Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250013, China

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Received Date: July 01, 2021
Available Online: May 07, 2022

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Abstract

Abstract

With the improvement of people’s living standard, the number of patients with thromboembolism is increasing gradually. Among the existing thrombotic drugs, nattokinase attracts great attention due to its advantages of long half-life, strong specificity, small side effects, and can be taken orally directly. Based on the related research results at home and abroad, the structure features of nattokinase, the fibrinolytic activity and the mechanism of action of antithrombotic activity of NK are described. Also, the hard work in strain breeding, strain transformation for higher enzyme yield or better enzyme character and medium optimization are also summarized. Moreover, the physiological function of nattokinase are expounded. Finally, the challenges and future development trends of nattokinase application are prospected in order to provide theoretical basis for further research on nattokinase.
- nattokinase,
- Bacillus subtilis (natto),
- production by microbial fermentation,
- physiological function

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References (99)

References

[1]	MOZAFFARIAN D. Dietary and policy priorities for cardiovascular disease, diabetes, and obesity: A comprehensive review [J]. Circulation, 2016, 133(2): Circulationaha. 115.018585.
[2]	SUMI H, HAMADA H, TSUSHIMA H, et al. A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese natto; a typical and popular soybean food in the Japanese diet[J]. Experientia,1987,43(10):1110−1111. doi: 10.1007/BF01956052
[3]	DABBAGH F, NEGAHDARIPOUR M, BERENJIAN A, et al. Nattokinase: Production and application[J]. Applied Microbiology and Biotechnology,2014,98(22):9199−9206. doi: 10.1007/s00253-014-6135-3
[4]	FUJITA M, NOMURA K, HONG K, et al. Purification and characterization of a strong fibrinolytic enzyme (nattokinase) in the vegetable cheese natto, a popular soybean fermented food in Japan[J]. Biochemical and Biophysical Research Communications,1993,197(3):1340−1347. doi: 10.1006/bbrc.1993.2624
[5]	NAKAMURA T, YAMAGATA Y, ICHISHIMA E. Nucleotide sequence of the subtilisin NAT gene, aprN, of Bacillus subtilis (natto)[J]. Bioscience Biotechnology & Biochemistry,1992,56(11):1869−1871.
[6]	JENSEN G, LENNINGER M, ERO M P, et al. Consumption of nattokinase is associated with reduced blood pressure and von willebrand factor, a cardiovascular risk marker: Results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial[J]. Integrated Blood Pressure Control,2016,9:95−104. doi: 10.2147/IBPC.S99553
[7]	KIM J Y, GUM S N, PAIK J K, et al. Effects of nattokinase on blood pressure: A randomized, controlled trial[J]. Hypertension Research,2008,31(8):1583−1588. doi: 10.1291/hypres.31.1583
[8]	PARK K J, KANG J I, KIM T S, et al. The antithrombotic and fibrinolytic effect of natto in hypercholesterolemia rats[J]. Preventive Nutrition and Food Science,2012,17(1):78−82. doi: 10.3746/pnf.2012.17.1.078
[9]	KANG S J, LIM Y, KIM A J. Korean red ginseng combined with nattokinase ameliorates dyslipidemia and the area of aortic plaques in high cholesterol-diet fed rabbits[J]. Food Science & Biotechnology,2014,23(1):283−287.
[10]	TAKABAYASHI T, IMOTO Y, SAKASHITA M, et al. Nattokinase, profibrinolytic enzyme, effectively shrinks the nasal polyp tissue and decreases viscosity of mucus[J]. Allergology International: Official Journal of the Japanese Society of Allergology,2017,66(4):594−602. doi: 10.1016/j.alit.2017.03.007
[11]	WENG Y, YAO J, SPARKS S, et al. Nattokinase: An oral antithrombotic agent for the prevention of cardiovascular disease[J]. International Journal of Molecular Sciences,2017,18(3):523. doi: 10.3390/ijms18030523
[12]	PENG Y, YANG X, ZHANG Y. Microbial fibrinolytic enzymes: An overview of source, production, properties, and thrombolytic activity in vivo[J]. Applied Microbiology and Biotechnology,2005,69(2):126−132. doi: 10.1007/s00253-005-0159-7
[13]	YANAGISAWA Y, CHATAKE T, CHIBA-KAMOSHIDA K, et al. Purification, crystallization and preliminary X-ray diffraction experiment of nattokinase from Bacillus subtilis natto[J]. Acta Crystallographica Section F Structural Biology and Crystallization Communications,2010,66(12):1670−1673. doi: 10.1107/S1744309110043137
[14]	LIU Z, ZHAO H, HAN L, et al. Improvement of the acid resistance, catalytic efficiency, and thermostability of nattokinase by multisite-directed mutagenesis[J]. Biotechnology and Bioengineering,2019,116(8):1833−1843. doi: 10.1002/bit.26983
[15]	ZHENG Z L, ZUO Z Y, LIU Z G, et al. Construction of a 3D model of nattokinase, a novel fibrinolytic enzyme from Bacillus natto: A novel nucleophilic catalytic mechanism for nattokinase[J]. Journal of Molecular Graphics & Modelling,2005,23(4):373−380.
[16]	ZHENG Z L, YE M Q, ZUO Z Y, et al. Probing the importance of hydrogen bonds in the active site of the subtilisin nattokinase by site-directed mutagenesis and molecular dynamics simulation[J]. Biochemical Journal,2006,395(3):509−515. doi: 10.1042/BJ20050772
[17]	WU S, FENG C, ZHONG J, et al. Roles of S3 site residues of nattokinase on its activity and substrate specificity[J]. Journal of Biochemistry,2007,142(3):357−364. doi: 10.1093/jb/mvm142
[18]	MAHAJAN P M, NAYAK S, LELE S S. Fibrinolytic enzyme from newly isolated marine bacterium Bacillus subtilis ICTF-1: Media optimization, purification and characterization[J]. Journal of Bioscience and Bioengineering,2012,113(3):307−314. doi: 10.1016/j.jbiosc.2011.10.023
[19]	CHANDRASEKARAN S D, VAITHILINGAM M, SHANKER R, et al. Exploring the in vitro thrombolytic activity of nattokinase from a new strain Pseudomonas aeruginosa CMSS[J]. Jundishapur Journal of Microbiology,2015,8(10):e23567.
[20]	WEI X, LUO M, XU L, et al. Production of fibrinolytic enzyme from Bacillus amyloliquefaciens by fermentation of chickpeas, with the evaluation of the anticoagulant and antioxidant properties of chickpeas[J]. Journal of Agricultural & Food Chemistry,2011,59(8):3957−3963.
[21]	PENG Y, HUANG Q, ZHANG R H, et al. Purification and characterization of a fibrinolytic enzyme produced by Bacillus amyloliquefaciens DC-4 screened from douchi, a traditional Chinese soybean food[J]. Comparative Biochemistry and Physiology. B: Biochemistry and Molecular Biology,2003,134(1):45−52. doi: 10.1016/S1096-4959(02)00183-5
[22]	WANG C T, JI B P, LI B, et al. Purification and characterization of a fibrinolytic enzyme of Bacillus subtilis DC33, isolated from Chinese traditional Douchi [J]. Journal of Industrial Microbiology and Biotechnology, 2006, 33(9): 750-758.
[23]	KIM W. Purification and characterization of a fibrinolytic enzyme produced from Bacillus sp. strain CK 11-4 screened from Chungkook-Jang[J]. Applied & Environmental Microbiology,1996,62(7):2482−2488.
[24]	CHANG S P, KIM D H, LEE W Y, et al. Identification of fibrinogen-induced nattokinase WRL101 from Bacillus subtilis WRL101 isolated from Doenjang[J]. African Journal of Microbiology Research,2013,7(19):15−22.
[25]	KIM S H, CHOI N S. Purification and characterization of Subtilisin DJ-4 secreted by Bacillus sp. strain DJ-4 screened from Doen-Jang[J]. Journal of the Agricultural Chemical Society of Japan,2000,64(8):1722−1725.
[26]	DEVI C S, MOHANASRINIVASAN V, SHARMA P, et al. Production, purification and stability studies on nattokinase: A therapeutic protein extracted from mutant Pseudomonas aeruginosa CMSS isolated from bovine milk[J]. International Journal of Peptide Research and Therapeutics,2015,22(2):263−269.
[27]	WANG S L, CHEN H J, LIANG T W, et al. A novel nattokinase produced by Pseudomonas sp. TKU015 using shrimp shells as substrate[J]. Process Biochemistry,2009,44(1):70−76. doi: 10.1016/j.procbio.2008.09.009
[28]	VAITHILINGAM M, CHANDRASEKARAN S D, GUPTA S, et al. Extraction of nattokinase enzyme from Bacillus cereus isolated from rust[J]. National Academy Science Letters,2016,39(4):263−270. doi: 10.1007/s40009-016-0476-7
[29]	INATSU Y, NAKAMURA N, YURIKO Y, et al. Characterization of Bacillus subtilis strains in Thua nao, a traditional fermented soybean food in northern Thailand[J]. Letters in Applied Microbiology,2006,43(3):237−242. doi: 10.1111/j.1472-765X.2006.01966.x
[30]	KUMAR D J M, RAKSHITHA R, M ANNU V, et al. Production, optimization and characterization of fibrinolytic enzyme by Bacillus subtilis RJAS19[J]. Pakistan Journal of Biological Sciences,2014,17(4):529−534. doi: 10.3923/pjbs.2014.529.534
[31]	CHANG C T, FAN M H, KUO F C, et al. Potent fibrinolytic enzyme from a mutant of Bacillus subtilis IMR-NK1[J]. Journal of Agriculture and Food Chemistry,2000,48(8):3210−3216. doi: 10.1021/jf000020k
[32]	WANG S L, WU Y Y, LIANG T W. Purification and biochemical characterization of a nattokinase by conversion of shrimp shell with Bacillus subtilis TKU007[J]. New Biotechnology,2011,28(2):196−202. doi: 10.1016/j.nbt.2010.09.003
[33]	LUO Y, LI B O, JI H, et al. Effect of voybean varieties on the fibrinolytic activity and sensory characteristics of Douchi[J]. Journal of Food Processing and Preservation,2010,34:457−469. doi: 10.1111/j.1745-4549.2008.00297.x
[34]	LIU J, XING J, CHANG T, et al. Optimization of nutritional conditions for nattokinase production by Bacillus natto NLSSE using statistical experimental methods[J]. Process Biochemistry,2005,40(8):2757−2762. doi: 10.1016/j.procbio.2004.12.025
[35]	KIM C, RI K, CHOE S. A novel fibrinolytic enzymes from the Korean traditional fermented food-Jotgal: Purification and characterization[J]. Journal of Food Biochemistry,2020,44(7):e13255.
[36]	NIE G, ZHU Z, LIU F, et al. Co-production of nattokinase and poly (γ-glutamic acid) under solid-state fermentation using soybean and rice husk[J]. Brazilian Archives of Biology and Technology,2015,58(5):718−724. doi: 10.1590/S1516-89132015050172
[37]	SHIH M C, YANG K A I T U, SU S Y, et al. Optimization process of roasted broken black soybean natto using response surface methodology[J]. Journal of Food Processing and Preservation,2011,37(5):474−482.
[38]	GUO N, JIANG Y W, SONG X R, et al. Effect of Bacillus natto solid-state fermentation on the functional constituents and properties of Ginkgo seeds[J]. Journal of Food Biochemistry,2019,43(5):e12820. doi: 10.1111/jfbc.12820
[39]	DONG M Z, AN J Y, WANG L T, et al. Development of fermented chestnut with Bacillus natto: Functional and sensory properties[J]. Food Research International,2020,130:108941. doi: 10.1016/j.foodres.2019.108941
[40]	VONG W C, LIU S Q. Biovalorisation of okara (soybean residue) for food and nutrition[J]. Trends in Food Science & Technology,2016,52:139−147.
[41]	PAGNONCELLI M G B, FERNANDES M J, RODRIGUES C, et al. Nattokinases [M]. Current Developments in Biotechnology and Bioengineering, 2017: 509-526.
[42]	CAI D, ZHANG B, RAO Y, et al. Improving the utilization rate of soybean meal for efficient production of bacitracin and heterologous proteins in the aprA-deficient strain of Bacillus licheniformis[J]. Applied Microbiology and Biotechnology,2019,103(12):4789−4799. doi: 10.1007/s00253-019-09804-0
[43]	BERENJIAN A, MAHANAMA R, KAVANAGH J, et al. Nattokinase production: Medium components and feeding strategy studies[J]. Chemical Industry and Chemical Engineering Quarterly,2014,20(4):541−547. doi: 10.2298/CICEQ130928037B
[44]	YANG H, LIU Y, NING Y, et al. Characterization of an intracellular alkaline serine protease from Bacillus velezensis SW5 with fibrinolytic activity[J]. Current Microbiology,2020,77(8):1610−1621. doi: 10.1007/s00284-020-01977-6
[45]	MAHAJAN P M, GOKHALE S V, LELE S S. Production of nattokinase using Bacillus natto NRRL 3666: Media optimization, scale up, and kinetic modeling[J]. Food Science and Biotechnology,2010,19(6):1593−1603. doi: 10.1007/s10068-010-0226-4
[46]	TUAN N A, THUAN D H T, TAM T T M, et al. Determination the optimum fermentation in obtaining nattokinase by Bacillus subtilis natto[J]. International Journal of Innovation and Applied Studies,2015,13:663−668.
[47]	MAN L L, XIANG D J, ZHANG C L. Strain screening from traditional fermented soybean foods and induction of nattokinase production in Bacillus subtilis MX-6[J]. Probiotics and Antimicrobial Proteins,2019,11(1):283−294. doi: 10.1007/s12602-017-9382-7
[48]	KHURSADE P S, GALANDE S H, SHIVA KRISHNA P, et al. Stenotrophomonas maltophilia Gd2: A potential and novel isolate for fibrinolytic enzyme production[J]. Saudi Journal of Biological Sciences,2019,26(7):1567−1575. doi: 10.1016/j.sjbs.2018.10.014
[49]	MOULA ALI A M, BAVISETTY S C B. Purification, physicochemical properties, and statistical optimization of fibrinolytic enzymes especially from fermented foods: A comprehensive review[J]. International Journal of Biological Macromolecules,2020,163:1498−1517. doi: 10.1016/j.ijbiomac.2020.07.303
[50]	AVHAD D N, RATHOD V K. Ultrasound assisted production of a fibrinolytic enzyme in a bioreactor[J]. Ultrasonics Sonochemistry,2015,22:257−264. doi: 10.1016/j.ultsonch.2014.04.020
[51]	SINGH R, KUMAR M, MITTAL A, et al. Microbial enzymes: Industrial progress in 21st century[J]. 3 Biotech,2016,6(2):174. doi: 10.1007/s13205-016-0485-8
[52]	ZAHOOR, KHAN, MARYAM, et al. Bacillus tequilensis ZMS-2: A novel source of alkaline protease with antimicrobial, anti-coagulant, fibrinolytic and dehairing potentials [J]. Pakistan Journal of Pharmaceutical Sciences, 2019, 32(4(Supplementary)): 1913-1918.
[53]	CHITTE R R, DESHMUKH S V, KANEKAR P P. Production, purification, and biochemical characterization of a fibrinolytic enzyme from thermophilic Streptomyces sp. MCMB-379[J]. Applied Biochemistry and Biotechnology,2011,165(5-6):1406−13. doi: 10.1007/s12010-011-9356-2
[54]	KWON E Y, KIM K M, KIM M K, et al. Production of nattokinase by high cell density fed-batch culture of Bacillus subtilis[J]. Bioprocess and Biosystems Engineering,2011,34(7):789−793. doi: 10.1007/s00449-011-0527-x
[55]	LIU Z, ZHENG W, GE C, et al. High-level extracellular production of recombinant nattokinase in Bacillus subtilis WB800 by multiple tandem promoters [J]. BMC Microbiology, 2019, 19(1): 89.
[56]	PURWAENI E, RIANI C, RETNONINGRUM D S. Molecular characterization of bacterial fibrinolytic proteins from indonesian traditional fermented foods[J]. Protein J,2020,39(3):258−267. doi: 10.1007/s10930-020-09897-x
[57]	LIANG X, ZHANG L, ZHONG J, et al. Secretory expression of a heterologous nattokinase in Lactococcus lactis[J]. Applied Microbiology and Biotechnology,2007,75(1):95−101. doi: 10.1007/s00253-006-0809-4
[58]	HAN L, ZHANG L, LIU J, et al. Transient expression of optimized and synthesized nattokinase gene in melon fruit by agroinfiltration[J]. Plant Biotechnology,2015,32(2):175−180. doi: 10.5511/plantbiotechnology.15.0430a
[59]	LI X, WANG X, XIONG S, et al. Expression and purification of recombinant nattokinase in Spodoptera frugiperda cells[J]. Biotechnology Letter,2007,29(10):1459−1464. doi: 10.1007/s10529-007-9426-2
[60]	WU S M, FENG C, ZHONG J, et al. Enhanced production of recombinant nattokinase in Bacillus subtilis by promoter optimization[J]. World Journal of Microbiology & Biotechnology,2011,27(1):99−106.
[61]	CAI Y J, BAO W, JIANG S J, et al. Directed evolution improves the fibrinolytic activity of nattokinase from Bacillus natto[J]. FEMS Microbiology Letters,2011,325(2):155−161. doi: 10.1111/j.1574-6968.2011.02423.x
[62]	CUI W, SUO F, CHENG J, et al. Stepwise modifications of genetic parts reinforce the secretory production of nattokinase in Bacillus subtilis[J]. Microbial Biotechnology,2018,11(5):930−942. doi: 10.1111/1751-7915.13298
[63]	CHEN P T, CHAO Y P. Enhanced production of recombinant nattokinase in Bacillus subtilisby the elimination of limiting factors[J]. Biotechnology Letters,2006,28(19):1595−1600. doi: 10.1007/s10529-006-9126-3
[64]	WENG M, DENG X, JIEYUAN W U, et al. Thermostability of subtilisin nattokinase obtained by site-directed mutagenesis[J]. Wuhan University Journal of Natural Sciences,2014,19(3):229−234. doi: 10.1007/s11859-014-1006-4
[65]	DEEPAK V, PANDIAN S, KALISHWARALAL K, et al. Purification, immobilization, and characterization of nattokinase on PHB nanoparticles[J]. Bioresource Technology,2009,100(24):6644−6646. doi: 10.1016/j.biortech.2009.06.057
[66]	HSIEH C W, LU W C, HSIEH W C, et al. Improvement of the stability of nattokinase using γ-polyglutamic acid as a coating material for microencapsulation[J]. LWT-Food Science and Technology,2009,42(1):144−149. doi: 10.1016/j.lwt.2008.05.025
[67]	WU C, GAO C, LÜ S, et al. Construction of polylysine dendrimer nanocomposites carrying nattokinase and their application in thrombolysis[J]. Journal of Biomedical Materials Research Part A,2018,106(2):440−449. doi: 10.1002/jbm.a.36232
[68]	CHEN C, DUAN H, GAO C, et al. Non-covalent modification of thrombolytic agent nattokinase: Simultaneous improvement of fibrinolysis activity and enzymatic stability[J]. RSC Advances,2014,4(52):27422−27429. doi: 10.1039/C4RA02626H
[69]	YE W, WANG N, HU K, et al. Bio-inspired microcapsule for targeted antithrombotic drug delivery[J]. RSC Advances,2018,8(48):27253−27259. doi: 10.1039/C8RA04273J
[70]	REN L, WANG X, WU H, et al. Conjugation of nattokinase and lumbrukinase with magnetic nanoparticles for the assay of their thrombolytic activities[J]. Journal of Molecular Catalysis B:Enzymatic,2010,62(2):190−196. doi: 10.1016/j.molcatb.2009.10.009
[71]	JI M, CHEN X, LUO J, et al. Improved blood compatibility of polysulfone membrane by anticoagulant protein immobilization[J]. Colloids and surfaces B, Biointerfaces,2019,175:586−595. doi: 10.1016/j.colsurfb.2018.12.026
[72]	ZHANG X, LYU X, TONG Y, et al. Chitosan/casein based microparticles with a bilayer shell-core structure for oral delivery of nattokinase[J]. Food & Function,2020,11(12):10799−10816.
[73]	ARSALAN A, YOUNUS H. Enzymes and nanoparticles: Modulation of enzymatic activity via nanoparticles [J]. International Journal of Biological Macromolecules, 2018, 118(Pt B): 1833-1847.
[74]	LAW D, ZHANG Z. Stabilization and target delivery of nattokinase using compression coating[J]. Drug Development & Industrial Pharmacy,2007,33(5):495−503.
[75]	DONG X Y, KONG F P, YUAN G Y, et al. Optimisation of preparation conditions and properties of phytosterol liposome-encapsulating nattokinase[J]. Natural Product Research,2012,26(6):548−556. doi: 10.1080/14786419.2010.528759
[76]	FUJITA M, HONG K, ITO Y, et al. Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat[J]. Biological & Pharmaceutical Bulletin,1995,18(10):1387−1391.
[77]	KAMIYA S, HAGIMORI M, OGASAWARA M, et al. In vivo evaluation method of the effect of nattokinase on carrageenan-induced tail thrombosis in a rat model[J]. Acta Haematologica,2010,124(4):218−224. doi: 10.1159/000321518
[78]	GUO H, BAN Y H, CHA Y, et al. Comparative anti-thrombotic activity and haemorrhagic adverse effect of nattokinase and tissue-type plasminogen activator[J]. Food Science and Biotechnology,2019,28(5):1535−1542. doi: 10.1007/s10068-019-00580-1
[79]	SUMI H, YANAGISAWA Y, YATAGAI C, et al. Natto Bacillus as an oral fibrinolytic agent: Nattokinase activity and the ingestion effect of Bacillus subtilis natto[J]. Food Science & Technology International Tokyo,2004,10(1):17−20.
[80]	FUJITA M, OHNISHI K, TAKAOKA S, et al. Antihypertensive effects of continuous oral administration of nattokinase and its fragments in spontaneously hypertensive rats[J]. Biological & Pharmaceutical Bulletin,2011,34(11):1696−1701.
[81]	LEE B H, LAI Y S, WU S C. Antioxidation, angiotensin converting enzyme inhibition activity, nattokinase, and antihypertension of Bacillus subtilis (natto)-fermented pigeon pea[J]. Journal of Food and Drug Analysis,2015,23(4):750−757. doi: 10.1016/j.jfda.2015.06.008
[82]	SUWANMANON K, HSIEH P C. Effect of gamma-aminobutyric acid and nattokinase-enriched fermented beans on the blood pressure of spontaneously hypertensive and normotensive Wistar-Kyoto rats[J]. Journal of Food and Drug Analysis,2014,22(4):485−491. doi: 10.1016/j.jfda.2014.03.005
[83]	MURAKAMI K, YAMANAKA N, OHNISHI K, et al. Inhibition of angiotensin I converting enzyme by subtilisin NAT (nattokinase) in natto, a Japanese traditional fermented food[J]. Food & Function,2012,3(6):674−678.
[84]	IBE S, YOSHIDA K, KUMADA K, et al. Antihypertensive effects of natto, a traditional Japanese fermented food, in spontaneously hypertensive rats[J]. Food Science & Technology Research,2009,15(2):199−202.
[85]	WEBER M A, SCHIFFRIN E L, WHITE W B, et al. Clinical practice guidelines for the management of hypertension in the community a statement by the american society of hypertension and the international society of hypertension[J]. Journal of Clinical Hypertension,2014,16(1):14−26. doi: 10.1111/jch.12237
[86]	LIN Y. A clinical study on the effect of nattokinase on carotid artery atherosclerosis and hyperlipidaemia[J]. Chinese Medical Journal,2017,97(26):2038−2045.
[87]	WU D J, LIN C S, LEE M Y. Lipid-lowering effect of nattokinase in patients with primary hypercholesterolemia[J]. Acta Cardiologica Sinica,2009,25(1):26−30.
[88]	谢嵩, 于宗琴, 刘秀菊. 纳豆激酶的制备及其降血脂功效研究[J]. 中国生化药物杂志,2015,35(1):17−20. [XIE S, YU Z, LIU X. Preparation of nattokinase and study on its hypolipidemic effect[J]. Chinese Journal of Biochemical Pharmaceutics,2015,35(1):17−20. XIE S, YU Z, LIU X. Preparation of nattokinase and study on its hypolipidemic effect [J]. Chinese Journal of Biochemical Pharmaceutics. 2015, 35(1): 17–20.
[89]	YANG N C, CHOU C W, CHEN C Y, et al. Combined nattokinase with red yeast rice but not nattokinase alone has potent effects on blood lipids in human subjects with hyperlipidemia[J]. Asia Pacific Journal of Clinical Nutrition,2009,18(3):310−317.
[90]	FOGACCI F, BANACH M, MIKHAILIDIS D P, et al. Safety of red yeast rice supplementation: A systematic review and meta-analysis of randomized controlled trials [J]. Pharmacological Research, 2019, 143(1-16).
[91]	YOO H J, KIM M, LEE A, et al. The effects of nattokinase supplementation on collagen-epinephrine closure time, prothrombin time and activated partial thromboplastin time in nondiabetic and hypercholesterolemic subjects[J]. Food & Function,2019,10(5):2888−2893.
[92]	BHATT P C, PATHAK S, KUMAR V, et al. Attenuation of neurobehavioral and neurochemical abnormalities in animal model of cognitive deficits of Alzheimer’s disease by fermented soybean nanonutraceutical[J]. Inflammopharmacology,2018,26(1):105−118. doi: 10.1007/s10787-017-0381-9
[93]	AHMED H H, FADL N N, EL-SHAMY K A, et al. Miracle enzymes serrapeptase and nattokinase mitigate neuroinﬂammation and apoptosis associated with Alzheimer's disease in experimental model[J]. World Journal of Pharmacy and Pharmaceutical Sciences,2014,3(2):876−891.
[94]	TAKANO A, HIRATA A, OGASAWARA K, et al. Posterior vitreous detachment induced by nattokinase (subtilisin nat): A novel enzyme for pharmacologic vitreolysis[J]. Investigative Ophthalmology & Visual Science,2006,47(5):2075−2079.
[95]	YAN Y, WANG Y, QIAN J, et al. Nattokinase crude extract inhibits hepatocellular carcinoma growth in mice[J]. Journal of Microbiology and Biotechnology,2019,29(8):1281−1287. doi: 10.4014/jmb.1812.12058
[96]	YANG H J, KIM M J, KWON D Y, et al. Combination of aronia, red ginseng, shiitake mushroom and nattokinase potentiated insulin secretion and reduced insulin resistance with improving gut microbiome dysbiosis in insulin deficient type 2 diabetic rats[J]. Nutrients,2018,10(7):948−967. doi: 10.3390/nu10070948
[97]	WEI X, LUO M, LIU H. Preparation of the antithrombotic and antimicrobial coating through layer-by-layer self-assembly of nattokinase-nanosilver complex and polyethylenimine[J]. Colloids and Surfaces B, Biointerfaces,2014,116:418−423. doi: 10.1016/j.colsurfb.2014.01.034
[98]	GOSHUA G, PINE A B, MEIZLISH M L, et al. Endotheliopathy in COVID-19-associated coagulopathy: Evidence from a single-centre, cross-sectional study[J]. The Lancet Haematology,2020,7(8):e575−e582. doi: 10.1016/S2352-3026(20)30216-7
[99]	REN B, YAN F, DENG Z, et al. Extremely high incidence of lower extremity deep venous thrombosis in 48 patients with severe COVID-19 in Wuhan[J]. Circulation,2020,142(2):181−183. doi: 10.1161/CIRCULATIONAHA.120.047407

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