Neurog1-Derived Peptides RMNE1 and DualPep-Shine Penetrate the Skin and Inhibit Melanin Synthesis by Regulating MITF Transcription

Int J Mol Sci. 2023 Mar 24;24(7):6158. doi: 10.3390/ijms24076158.

Abstract

Anti-pigmentation peptides have been developed as alternative skin-lightening agents to replace conventional chemicals that have adverse effects on the skin. However, the maximum size of these peptides is often limited by their low skin and cell penetration. To address this issue, we used our intra-dermal delivery technology (IDDT) platform to identify peptides with hypo-pigmenting and high cell-penetrating activity. Using our cell-penetrating peptides (CPPs) from the IDDT platform, we identified RMNE1 and its derivative RMNE3, "DualPep-Shine", which showed levels of α-Melanocyte stimulating hormone (α-MSH)-induced melanin inhibition comparable to the conventional tyrosinase inhibitor, Kojic acid. In addition, DualPep-Shine was delivered into the nucleus and regulated the gene expression levels of melanogenic enzymes by inhibiting the promoter activity of microphthalmia-associated transcription factor-M (MITF-M). Using a 3D human skin model, we found that DualPep-Shine penetrated the lower region of the epidermis and reduced the melanin content in a dose-dependent manner. Furthermore, DualPep-Shine showed high safety with little immunogenicity, indicating its potential as a novel cosmeceutical ingredient and anti-pigmentation therapeutic agent.

Keywords: DualPep-Shine; Neoderm; Neurog1; cell-penetrating peptide; melanin; microphthalmia-associated transcription factor; skin penetration.

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors* / chemistry
  • Basic Helix-Loop-Helix Transcription Factors* / pharmacology
  • Cell-Penetrating Peptides* / chemistry
  • Cell-Penetrating Peptides* / pharmacology
  • Epidermis / drug effects
  • Epidermis / metabolism
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Melanins* / antagonists & inhibitors
  • Melanocytes* / drug effects
  • Melanocytes* / metabolism
  • Melanoma, Experimental
  • Microphthalmia-Associated Transcription Factor* / genetics
  • Nerve Tissue Proteins* / chemistry
  • Nerve Tissue Proteins* / pharmacology
  • Skin Lightening Preparations* / chemistry
  • Skin Lightening Preparations* / pharmacology
  • Skin Pigmentation* / drug effects
  • Transcription, Genetic* / drug effects
  • alpha-MSH / antagonists & inhibitors
  • alpha-MSH / metabolism

Substances

  • Melanins
  • Mitf protein, mouse
  • Microphthalmia-Associated Transcription Factor
  • alpha-MSH
  • Cell-Penetrating Peptides
  • Skin Lightening Preparations
  • NEUROG1 protein, human
  • Nerve Tissue Proteins
  • Basic Helix-Loop-Helix Transcription Factors