Biocompatible exosomes derived from Pinctada martensii mucus for therapeutic melanin regulation via α-MSH/NF-κB/MITF pathway.

Abnormal melanin production can lead to various pigmentary disorders, which significantly affect patients' quality of life and overall health. However, current clinical melanogenesis inhibitors have adverse side effects such as skin dryness, itching, erythema, etc. In this study, we used naturally isolated exosomes derived from Pinctada martensii mucus (PMMEXOs) and investigated the effects on melanin synthesis based on B16-F10 melanoma cells and zebrafish. We demonstrated that PMMEXOs effectively inhibited melanin production while exhibiting excellent biocompatibility. To elucidate the underlying mechanisms, RNA sequencing and bioinformatics analysis were employed, identifying 556 differentially expressed genes associated with PMMEXOs treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the involvement of the NF-κB signaling pathway in the regulation of melanogenesis. Further mechanistic studies confirmed that PMMEXOs significantly reduced tyrosinase activity and melanin content, accompanied by the downregulation of critical melanogenesis-related genes and proteins, including MITF, TYR, TYRP-1 and TRP-2. Notably, the anti-melanogenic effects of PMMEXOs were mediated by activation of the NF-κB signaling pathway, underscoring their regulatory role in melanin biosynthesis. Additionally, microRNA (miRNA) sequencing of PMMEXOs identified specific miRNAs implicated in immune regulation and modulation of the NF-κB pathway, further supporting their mechanistic involvement in melanin inhibition. These findings collectively position PMMEXOs as a promising and innovative therapeutic strategy for the prevention and treatment of pigmentary disorders such as melasma, age spots and wrinkles.