Protective effects of nattokinase against microvasculopathy and neuroinflammation in diabetic retinopathy

Abstract

AimsDiabetic retinopathy (DR) is a significant global public health concern. Alternative, safe, and cost‐effective pharmacologic approaches are warranted. We aimed to investigate the therapeutic potential of nattokinase (NK) for early DR and the underlying molecular mechanism.MethodsA mouse model of diabetes induced by streptozotocin was utilized and NK was administered via intravitreal injection. Microvascular abnormities were evaluated by examining the leakage from blood–retinal barrier dysfunction and loss of pericytes. Retinal neuroinflammation was examined through the assessment of glial activation and leukostasis. The level of high mobility group box 1 (HMGB1) and its downstream signaling molecules was evaluated following NK treatment.ResultsNK administration significantly improved the blood–retinal barrier function and rescued pericyte loss in the diabetic retinas. Additionally, NK treatment inhibited diabetes‐induced gliosis and inflammatory response and protected retinal neurons from diabetes‐induced injury. NK also improved high glucose‐induced dysfunction in cultured human retinal micrangium endothelial cells. Mechanistically, NK regulated diabetes‐induced inflammation partially by modulating HMGB1 signaling in the activated microglia.ConclusionsThis study demonstrated the protective effects of NK against microvascular damages and neuroinflammation in the streptozotocin‐induced DR model, suggesting that NK could be a potential pharmaceutical agent for the treatment of DR.

Nattokinase: Insights into Biological Activity, Therapeutic Applications, and the Influence of Microbial Fermentation

“…In a murine model of oxygen-induced retinal pathology, nattokinase attenuates neuroinflammation and inhibits pathological neovascularization by activating the Nrf2/HO-1 signaling pathway and modulating neuroglial activation [45]. For diabetic macular edema, commonly employed treatments involve injections of anti-vascular endothelial growth factor agents or corticosteroids, but there are still side effects such as drug resistance, macular ischemia, and disease recurrence [44,47,48]. Maintaining the integrity of the blood-retinal barrier (BRB) is fundamental in treating DR. Huang et al [47] demonstrated that nattokinase interferes with downstream signaling by inhibiting the expression of high-mobility group protein 1, thereby enhancing BRB function.…”

“…For diabetic macular edema, commonly employed treatments involve injections of anti-vascular endothelial growth factor agents or corticosteroids, but there are still side effects such as drug resistance, macular ischemia, and disease recurrence [44,47,48]. Maintaining the integrity of the blood-retinal barrier (BRB) is fundamental in treating DR. Huang et al [47] demonstrated that nattokinase interferes with downstream signaling by inhibiting the expression of high-mobility group protein 1, thereby enhancing BRB function. This heralds the potential of nattokinase as a prospective alternative medication for treating diabetic retinal pathologies.…”