The Apocarotenoid Bixin Protects Mouse Skin against UV-induced Damage in an NRF2-dependent Manner

Abstract

Skin barrier function and integrity can be impaired as a result of exposure to environmental stressors, including solar ultra violet (UV) radiation. UV induces oxidative stress, inflammation, premature ageing, and cancer. Therefore, there is a need to find effective and safe strategies to protect the skin from these deleterious effects. An effective strategy to prevent UV damage involves activation of the transcription factor nuclear factor-E2-related factor 2 (NRF2) to induce cellular stress responses and damage repair. We recently characterized the apocarotenoid bixin, and FDA-approved natural food colorant from the seeds of the achiote tree (Bixa orellana), as a safe and potent NRF2 activator. In this study, we tested the feasibility of enhancing NRF2-dependent skin protection using a topical bixin formulation in a model for acute UV-induced skin damage and UV-induced hair graying. Nrf2+/+ and Nrf2-/- SKH-I hairless mice (acute skin damage) or C57BL/6J mice (hair graying) were treated twice with a topical bixin formulation 48 h and 24 h before exposure to UV. Skin tissues were harvested at 24 h (acute skin damage) or 2 weeks (hair graying) post-exposure and analyzed by immunoblotting and immunohistochemistry. We observed that bixin activated cutaneous expression of NRF2 and its target genes, and limited photodamage in Nrf2+/+ but not Nrf2-/- mice. Moreover, bixin reduced inflammation, oxidative damage, and apoptosis in the epidermis of Nrf2+/+ SKH-I mice. Consistently, bixin prevented UV-induced hair graying in Nrf2+/+ C57BL/6J mice. These results suggest that bixin-based interventions may be useful for NRF2-dependent skin protection against environmental insults.