An Elemental Miracle for Reducing Vascular Inflammation

Cardiovascular diseases (CVD) have long been the leading cause of death worldwide. While traditional medications are effective, many are exploring natural supplements to support vascular health. Among these, nattokinase (NK), as a non-animal, active, and scientifically assured ingredient, has garnered attention for its anti-thrombotic and anti-inflammatory properties.

Nattokinase Recap

Nattokinase is a protein enzyme derived from Bacillus subtilis found in natto, a legendary fermented soybean discovered from a long history in Japan. It is known for multiple benefits, such as blood clots dissolving, improving circulation, inflammatory reduction and the regulation of blood pressure.

Functional Insights - Vascular Inflammatory Protection

Endothelial cells (ECs) form the inner lining of blood vessels and play a central role in vascular homeostasis, inflammation, and atherosclerosis development. Hence, the inflammasome activity, gene regulation, autophagy and necroptosis effects of Nattokinase are examined in the study involving endothelial cells and a mouse model. This study aimed to determine:

Does Nattokinase regulate gene expression in endothelial inflammation?
Can Nattokinase enhance autophagy?
Is Nattokinase capable of reducing inflammasome activation and necroptosis?
Can Nattokinase mitigate vascular inflammation in vivo?

Key Results

Gene Regulation and Autophagy

Nattokinase increased Serum Response Factor (SRF) and Thrombospondin 1 (THBS1) expression, which acts as the switch for autophagy and inflammation control.

Nattokinase elevated LC3, beclin-1, and p62, indicating the activation of autophagy that clears damaged structures, supporting endothelial health and the indication of alleviation of inflammation effects.

Inhibition of Inflammasome and Necroptosis Responses

Inflammasome is a protein complex that triggers inflammation response; Necroptosis, on the other hand, is a type of cell death that can exacerbate inflammation.
Nattokinase suppressed NLRP3, Apoptosis-associated speck-like protein containing a CARD (ASC), cleaved caspase-1, and necroptosis markers (p-RIP1, p-RIP3, p-MLKL).

Animal Model Evidence (2,000 and 4,000 FU/kg)

Lowered the expression of vascular adhesion molecules like Intercellular cell adhesion molecule 1 (ICAM-1), VCAM-1 (vascular) and E-Selectin in the TNF-α-induced mouse model. These molecules promote leukocyte adhesion when atherosclerosis progresses; the inhibition of which indicates a general alleviation of inflammatory response.
Aortic wall thickening indicates the chronic inflammation that happens in the vascular system, it would increase the risk of arterial stiffness and plaque formation; Nattokinase treatment reduces the aortic wall thickening, supporting the preventive effect that nattokinase involved, in inflammation-driven vascular diseases.

Takeaways

The study highlights nattokinase’s dual role in dissolving blood clots and protecting against vascular inflammation. According to previous research, nattokinase is long and well known for its capability of fibrinolysis, blood clots dissolving and vascular circulation improvement. The current study potentiates Nattokinase another pathway via modulation of specific genetic pathways - SRF and THBS1- to further activate autophagy and suppress inflammatory effects, in the vascular related inflammation and pre-atherosclerosis condition.

Reference

Hui-Wen Chiu et al., “Nattokinase attenuates endothelial inflammation through the activation of SRF and THBS1”, 2024

Full article at: https://doi.org/10.1016/j.ijbiomac.2024.131779