Morus alba L. root decreases melanin synthesis via sphingosine-1-phosphate signaling in B16F10 cells

Ethnopharmacological relevance: Morus alba L. has long been used for beauty in many Asian countries and regions, including anti-aging and hyperpigmentation.Aim of the study: This study aimed at the inhibitory effect of Morus alba L. root on melanogenesis in B16F10 melanoma cells and the mechanism involved.Materials and methods: This study evaluated the anti-melanogenic effect of Morus alba L. root extract (MAR) on B16F10 melanoma cells by assessing cell viability, melanin accumulation, cellular tyrosinase activity, intra/inter-cellular S1P levels, cellular S1P-related metabolic enzyme activity, and western blot analysis. In addition, the potential S1P lyase (S1PL) inhibitory constituents in MAR were identified by LC-MS/MS.Results: Without affecting the viability of B16F10 melanoma cells, MAR inhibited intracellular tyrosinase activity in a dose-dependent manner, thereby reducing the accumulation of melanin. MAR also downregulated the expression level of MITF via activating the ERK signaling pathway. Furthermore, MAR increased the intra/inter-cellular S1P by inhibiting S1PL. Several compounds with inhibitory S1PL activity have been identified in MAR, such as mulberroside A and oxyresveratrol.Conclusions: The anti-melanogenic effects of MAR mainly involve promoting MITF degradation mediated via S1P-S1PR3-ERK signaling through increasing cellular S1P levels by inhibiting S1PL activity.

Automated summary

Morus alba L. root extract (MAR) has an inhibitory effect on melanogenesis in B16F10 melanoma cells by promoting MITF degradation mediated via S1P-S1PR3-ERK signaling and increasing cellular S1P levels through inhibiting S1PL activity.