Melanogenesis inhibition and anti-inflammation is essential for pigment-clearance in melasma treated by low-fluence Q-switched nd: YAG 1064 nm laser

Melasma is a common acquired disorder of disfiguring hyperpigmentation and has attracted increasing attention in the field of medical aesthetics due to its high risk for recurrence and difficulty in treatment. Low-fluence Q-switched Nd: YAG 1064 nm (LFQSNY) laser is a commonly used phototherapy clinical for melasma at present, however, the mechanism underlying the photomanipulation remains unclear. Herein, this study aims to elucidate the potential mechanisms underlying the LFQSNY laser treatment. B16F10 murine melanoma cells were subjected to LFQSNY laser irradiation for evaluating melanin synthesis, tyrosinase activity, and melanogenic gene expression. RNA-seq and dual-luciferase reporter assays were utilized to dissect the interaction of DHX9 with TRIB3. C57BL/6J mice skin were irradiated for further assessments. Additionally, M1-polarized RAW264.7 macrophages were treated by laser to investigate inflammatory-mediator production and phagocytic capacity. LFQSNY laser irradiation significantly attenuated melanin production in cells via upregulating DHX9 and repressing TRIB3 through promoter binding, which emerged as a critical determinant of melanogenesis suppression. Furthermore, LFQSNY laser reduced the inflammatory factors and enhanced the phagocytic activity in macrophages, resulting in the anti-inflammatory activities and pigment-clearing. Our findings reveal that LFQSNY laser inhibits the melanogenesis of melanocytes and enhances the effect of anti-inflammation for improves pigment-clearance in melasma via a non-thermal photobiomodulation. The insights provide a mechanistic rationale for enhancing clinical efficacy of LFQSNY laser-therapy in melasma.