6-Bromo-Indirubin-3'-Oxime (6BIO) mitigates oxidative stress and immune dysregulation to promote melanocyte regeneration in vitiligo.

Abstract

BACKGROUND: 6-bromo-indirubin-3-oxime (6BIO) is a small compound with known antioxidative and immunomodulatory properties, yet its efficacy in vitiligo remains unexplored. OBJECTIVES: To investigate therapeutic potential of 6BIO in modulating oxidative stress, immune response, and melanogenesis through in vitro and in vivo models. METHODOLOGY: RESULTS: 6BIO significantly decreased intracellular ROS levels, promoted melanin synthesis and nuclear localization of Nrf2 along with upregulation of antioxidant target genes in melanocytes. In vivo, 6BIO reduced epidermal thickness, decreased CD8T-cell infiltration and IFN-γ expression, lowered ROS accumulation while promoting regeneration of hair shafts, melanocyte repopulation and tyrosinase expression. In PBMCs from vitiligo patients, 6BIO decreased IFN-γ, a pro-inflammatory cytokine and increased anti-inflammatory IL-10, leading to a significantly reduced IFN-γ:IL-10 ratio. CONCLUSION: 6BIO exerts potent antioxidative, immunomodulatory and melanogenic effects in both cellular and animal models of vitiligo. These findings highlight the therapeutic potential of 6BIO as a novel treatment strategy for restoring pigmentation and immune balance in vitiligo.