PEP-1 fused to glutathione peroxidase from Trichoderma reesei: a safe and effective antioxidant active ingredient for cutaneous applications

Skin aging is associated with an increase in the generation of reactive oxygen species (ROS), leading to progressive cellular damage. Simultaneously, the skin's antioxidant mechanisms become less effective, compromising its defense capacity. Although the use of antioxidant enzymes in cosmetic and dermatological products is promising, the topical application of these molecules is hindered by their physicochemical characteristics. An effective alternative is using cell-penetrating peptides (CPPs), which facilitate the transduction of macromolecules, including enzymes, through the skin barrier. Here, an antioxidant system composed of the glutathione peroxidase enzyme from the fungus Trichoderma reesei (TrGPx) fused to the CPP Pep-1 (PEP1-TrGPx) was developed as an alternative active antioxidant ingredient for skin treatment. The efficacy and safety of this system were evaluated as a potential cosmetic and dermatological application. The results showed that PEP1-TrGPx was effectively delivered and protected human keratinocyte (HaCaT) epidermal cells against oxidative stress induced by H₂O₂ at low concentrations without showing a significant cytotoxic effect. Furthermore, the system demonstrated no potential for skin or ocular irritation. These findings suggest that PEP1-TrGPx is a promising, stable, safe, and effective active ingredient with great potential for therapeutic and cosmetic applications. It offers an effective strategy for skin care and mitigating oxidative stress-related damage associated with aging.