Research progress on the utilisation of embedding technology and suitable delivery systems for improving the bioavailability of nattokinase: A review

Zhou, Xueqin; Liang-zhong, Liu; Zeng, Xurui

doi:10.1016/j.foostr.2021.100219

Cited by 12 publications

(5 citation statements)

References 77 publications

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“…However, a variety of other enzymes have thrombolytic activity [ 916–919 ]. Considered less potent and safer than post-stroke ‘clotbusters’ such as tPA [ 920 ], nattokinase is a fibrinolytic [ 921–923 ] (and amyloid-degrading [ 924 ]), orally available despite having to pass through the gut wall [ 925–931 ], safe [ 932 , 933 ], serine protease enzyme from Bacillus subtilis (an organism which may itself be of value [ 934 ]). It is found naturally in the Japanese fermented food nattō [ 751 , 928 , 935–939 ], (which is also a source of vitamin K, and has antiviral properties directly [ 940 ]).…”

Section: Anticoagulants Platelet Inhibitors and The Triple Treatmentmentioning

confidence: 99%

The potential role of ischaemia–reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications

Kell

2022

Biochemical Journal

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Ischaemia–reperfusion (I–R) injury, initiated via bursts of reactive oxygen species produced during the reoxygenation phase following hypoxia, is well known in a variety of acute circumstances. We argue here that I–R injury also underpins elements of the pathology of a variety of chronic, inflammatory diseases, including rheumatoid arthritis, ME/CFS and, our chief focus and most proximally, Long COVID. Ischaemia may be initiated via fibrin amyloid microclot blockage of capillaries, for instance as exercise is started; reperfusion is a necessary corollary when it finishes. We rehearse the mechanistic evidence for these occurrences here, in terms of their manifestation as oxidative stress, hyperinflammation, mast cell activation, the production of marker metabolites and related activities. Such microclot-based phenomena can explain both the breathlessness/fatigue and the post-exertional malaise that may be observed in these conditions, as well as many other observables. The recognition of these processes implies, mechanistically, that therapeutic benefit is potentially to be had from antioxidants, from anti-inflammatories, from iron chelators, and via suitable, safe fibrinolytics, and/or anti-clotting agents. We review the considerable existing evidence that is consistent with this, and with the biochemical mechanisms involved.

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Section: Anticoagulants Platelet Inhibitors and The Triple Treatmentmentioning

confidence: 99%

The potential role of ischaemia–reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications

Kell

2022

Biochemical Journal

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“…Nattokinase is a thrombolytic drug with advantages over urokinase, streptokinase, and tissue plasminogen activator, including a low price, high efficiency, and lack of toxicity (Zhou et al, 2021). However, its taste limits its consumption.…”

Section: Discussionmentioning

confidence: 99%

Construction and functional analysis of nattokinase-producing cucumber obtained by the CRISPR-Cas9 system

Zhang

et al. 2023

AAlim

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Nattokinase (NK) is effective in the prevention and treatment of cardiovascular disease. Cucumber is rich in nutrients with low sugar content and is safe for consumption. The aim of this study was to construct a therapeutic cucumber that can express NK, which can prevent and alleviate cardiovascular diseases by consumption. Because the Bitter fruit (Bt) gene contributes to bitter taste but has no obvious effect on the growth and development of cucumber, so the NK-producing cucumber was constructed by replacing the Bt gene with NK by using CRISPR/Cas9. The pZHY988-Cas9-sgRNA and pX6-LHA-U6-NK-T-RHA vectors were constructed and transformed into Agrobacterium tumefaciens EHA105, which was transformed into cucumber by floral dip method. The crude extract of NK-producing cucumber had significant thrombolytic activity in vitro. In addition, treatment with the crude extract significantly delayed thrombus tail appearance, and the thrombin time of mice was much longer than that of normal mice. The degrees of coagulation and blood viscosity as well as hemorheological properties improved significantly after crude extract treatment. These findings show that NK-producing cucumber can effectively alleviate thrombosis and improve blood biochemical parameters, providing a new direction for diet therapy against cardiovascular diseases.

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“…Our previous studies have shown that FGFC1 is a rare marine Bisindole alkaloid fibrinolytic compound with isoindolylopyran as its mother nucleus connecting isoamyl alkene chain and valerate group, which is completely different from bacterial and fungicidal fibrinolytic enzymes such as nattokinase(NK), boletus pseudocalopus fibrinolytic enzyme (BPFE) [ 42 , 43 , 44 , 45 , 46 ]. NK is a single-chain polypeptide serine protease composed of 275 amino acid residues with a molecular weight of 27.7 kDa [ 47 ]. NK regulates fibrinolysis directly or indirectly through the following mechanisms: NK directly degrades fibrin into small-molecular peptides and amino acids; activating the conversion of pro-urokinase to urokinase; inactivating PAI-1 to enhance fibrinolysis [ 47 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

“…NK is a single-chain polypeptide serine protease composed of 275 amino acid residues with a molecular weight of 27.7 kDa [ 47 ]. NK regulates fibrinolysis directly or indirectly through the following mechanisms: NK directly degrades fibrin into small-molecular peptides and amino acids; activating the conversion of pro-urokinase to urokinase; inactivating PAI-1 to enhance fibrinolysis [ 47 , 48 ]. However, NK is a protease sensitive to gastric acid.…”

Section: Discussionmentioning

confidence: 99%

“…However, NK is a protease sensitive to gastric acid. If it is taken orally, the purpose of thrombolysis cannot be achieved [ 47 ]. BPFE is purified from fruiting bodies of wild-growing mushroom Boletus pseudocalopus Hongo, composed of amino acid residues with a molecular weight of 63.5 kDa, while there are no studies that have evaluated the fibrinolytic mechanism of BPFE [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

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A Novel Marine Pyran-Isoindolone Compound Enhances Fibrin Lysis Mediated by Single-Chain Urokinase-Type Plasminogen Activator

et al. 2022

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Fungi fibrinolytic compound 1 (FGFC1) is a rare pyran-isoindolone derivative with fibrinolytic activity. The aim of this study was to further determine the effect of FGFC1 on fibrin clots lysis in vitro. We constructed a fibrinolytic system containing single-chain urokinase-type plasminogen activator (scu-PA) and plasminogen to measure the fibrinolytic activity of FGFC1 using the chromogenic substrate method. After FITC-fibrin was incubated with increasing concentrations of FGFC1, the changes in the fluorescence intensity and D-dimer in the lysate were measured using a fluorescence microplate reader. The fibrin clot structure induced by FGFC1 was observed and analyzed using a scanning electron microscope and laser confocal microscope. We found that the chromogenic reaction rate of the mixture system increased from (15.9 ± 1.51) × 10−3 min−1 in the control group to (29.7 ± 1.25) × 10−3 min−1 for 12.8 μM FGFC1(p < 0.01). FGFC1 also significantly increased the fluorescence intensity and d-dimer concentration in FITC fibrin lysate. Image analysis showed that FGFC1 significantly reduced the fiber density and increased the fiber diameter and the distance between protofibrils. These results show that FGFC1 can effectively promote fibrin lysis in vitro and may represent a novel candidate agent for thrombolytic therapy.

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Research progress on the utilisation of embedding technology and suitable delivery systems for improving the bioavailability of nattokinase: A review

Cited by 12 publications

References 77 publications

The potential role of ischaemia–reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications

The potential role of ischaemia–reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications

Construction and functional analysis of nattokinase-producing cucumber obtained by the CRISPR-Cas9 system

A Novel Marine Pyran-Isoindolone Compound Enhances Fibrin Lysis Mediated by Single-Chain Urokinase-Type Plasminogen Activator

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