Glutathione Trisulphide Suppresses UVB-Induced Melanogenesis and Improves Skin Brightness in a Three-Dimensional Skin Model

Ultraviolet B (UVB) irradiation induces hyperpigmentation and contributes to skin photoaging. Glutathione trisulphide (GSSSG), a naturally occurring supersulphide with anti-inflammatory and antioxidant properties, has been shown to suppress α-melanocyte-stimulating hormone-induced melanogenesis and improve skin brightness. However, its efficacy under physiologically relevant UVB-induced pigmentation conditions and its skin-brightening potential in human skin-like systems remain unclear. Therefore, this study evaluated the anti-melanogenic effects of GSSSG in UVB-stimulated melanogenesis and assessed its skin-brightening efficacy in a three-dimensional (3D) skin model while investigating the relationship between melanogenesis and intracellular endogenous supersulphide levels. UVB irradiation increased melanin production while decreasing intracellular supersulphide levels. GSSSG suppressed UVB-induced melanogenesis and restored intracellular supersulphide levels. Furthermore, Cars2 knockdown reduced intracellular supersulphide levels and melanin production, suggesting a role for endogenous supersulphides in pigmentation. In addition, 0.1% GSSSG significantly improved skin brightness in a 3D skin model. These findings demonstrate the efficacy of GSSSG in both UVB-induced melanogenesis and a human skin-like model and suggest that supersulphides play context-dependent roles in melanogenesis, suppressing excessive pigmentation while supporting physiological melanin synthesis.