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

J Ethnopharmacol. 2023 Jan 30:301:115848. doi: 10.1016/j.jep.2022.115848. Epub 2022 Oct 19.

Abstract

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.

Keywords: Anti-melanogenesis; B16F10 melanoma cell; Morus alba L. root extract; S1P; S1P regulatory enzyme.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Chromatography, Liquid
  • Melanins / metabolism
  • Melanoma*
  • Melanoma, Experimental* / metabolism
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Monophenol Monooxygenase
  • Morus*
  • Signal Transduction
  • Tandem Mass Spectrometry

Substances

  • Melanins
  • Monophenol Monooxygenase
  • sphingosine 1-phosphate
  • Microphthalmia-Associated Transcription Factor