Glabridin Promotes Melanosome Degradation and Alleviates Melanosome-Induced Mitochondrial Dysfunction in Keratinocytes via Autophagy

Methods

We investigated the effect of glabridin on melanosome degradation by measuring melanin content and PMEL17 protein levels. Autophagy activity was evaluated by mRNA sequencing, Western blot, and immunofluorescence. In vivo depigmenting efficacy was examined using epidermal skin equivalents and zebrafish embryos.

Additionally, ATP content and mitochondrial membrane potential were measured to determine whether glabridin ameliorates melanosome-induced mitochondrial dysfunction. Results: Glabridin promoted melanosome degradation in keratinocytes and exhibited depigmenting effects in both pigmented epidermal skin equivalents and zebrafish embryos. Mechanistically, glabridin activated autophagy, and pharmacological inhibition of autophagy blocked its depigmenting effects.

Additionally, we found that melanosome accumulation impaired mitochondrial function in keratinocytes, an effect that was reversed by glabridin. Conclusions: These findings demonstrate that glabridin promotes melanosome degradation via autophagy activation, which is associated with improved mitochondrial function, providing mechanistic insight into its skin-lightening effects.