Nattokinase Crude Extract Enhances Cutaneous Wound Healing

Nattokinase (NK) is a fibrinolytic enzyme produced by Bacillus subtilis. This enzyme comes from a traditional Japanese fermented food called natto, and has therapeutic effects in a variety of diseases including hypertension, Alzheimer's disease, and vitreoretinal disorders. Whether NK is effective in skin tissue regeneration is unclear. Using ultrafiltration membranes, we separated a cultured medium of Bacillus subtilis into samples of different molecular weights. Of all the components from the cultured medium of Bacillus subtilis, only the 10 kDa (K) to 100 K molecular weight components had NK activity; these components were named nattokinase crude extract (NCE). NCE demonstrated the ability to promote wound healing in mouse skin-resection injuries. Relative to the other ingredients in the cultured supernatant, NCE has a more pronounced effect on epidermal regeneration and angiogenesis. The expression levels of Oct-4 and Nanog in the skin tissue of the NCE-treated group were significantly higher. This study reveals a new role for NK in cutaneous wound healing and demonstrates that NCE extends the application of NK.