Isoimperatorin (ISO) reduces melanin content in keratinocytes via miR-3619/CSTB and miR-3619/CSTD axes.

Melanin metabolism disorders may cause severe impacts on the psychological and social activities of patients. Different from the other two steps of melanin metabolism, namely synthesis and transport, little has been known about the mechanism of melanin degradation. Isoimperatorin (ISO) suppressed the activity of tyrosinase, an essential enzyme in melanin biosynthesis, hence, we investigated the effects and mechanism of ISO in melanin reduction. ISO stimulation significantly reduces the melanin contents and PMEL 17 protein levels; meanwhile, the activity and the protein levels of two critical lysosomal enzymes, Cathepsin B and Cathepsin D, can be significantly increased by ISO treatment. MiR-3619 inhibited the expression of CSTB and CSTD, therefore affecting ISO-induced degradation of melanin. In summary, ISO reduces the melanin content via miR-3619/CSTB and miR-3619/CSTD axes. ISO could be a potent skin-whitening agent, which needs further in vivo and clinical investigation.