Lotus Sprout Extract Induces Selective Melanosomal Autophagy and Reduces Pigmentation

ABSTRACT Background Hyperpigmentation disorders are caused by the excess production and irregular accumulation of melanin. Existing treatments often have limited efficacy and adverse effects, necessitating the development of new skin‐brightening agents. Lotus sprout extract (LSE) was identified as a potential pigment‐correcting agent. However, the active compounds responsible for driving mechanisms related to this activity remain unknown. Aims This study aimed to investigate the effects of LSE and its active components, neferine and liensinine, on melanin accumulation and to understand how LSE reduces skin pigmentation. Methods Melanin accumulation was analyzed in MNT‐1 human melanoma cells and MelanoDerm human skin equivalents following neferine, liensinine, or LSE treatment. The effects of the compounds on different pathways regulating melanin levels were evaluated by gene expression, biochemical assays, and western blotting. Melanosome ultrastructure was monitored using transmission electron microscopy (TEM). Results Neferine and liensinine reduced melanin accumulation in MNT‐1 cells without downregulating melanogenesis‐related genes or inhibiting tyrosinase activity. Instead, these compounds increased autophagic flux, suggesting that the reduction in pigmentation was due to increased melanin degradation. LSE also reduced melanin accumulation and activated autophagy in normal human melanocytes and MelanoDerm tissue. Autophagosomes induced by LSE treatment contained only melanosomes, and structural changes in melanosomes suggested that LSE may disrupt melanosome maturation. Conclusion This study revealed a novel mechanism for LSE, neferine, and liensinine in reducing pigmentation, potentially through the induction of autophagy and subsequent melanosome degradation. These findings suggest that LSE and its enriched bioactive compounds could be promising agents for treating hyperpigmentation.