Pterostilbene inhibits melanogenesis, melanocyte dendricity and melanosome transport through cAMP/PKA/CREB pathway

Eur J Pharmacol. 2022 Oct 15:932:175231. doi: 10.1016/j.ejphar.2022.175231. Epub 2022 Aug 28.

Abstract

Pterostilbene is a trans stilbene compound, which is an effective component of herbaceous plants such as Dalbergia woods and Vaccinium. Although pterostilbene has many uses in anti-inflammatory, anti-oxidant and anti-tumor, its whitening effect is drawing more and more attention, the mechanism of melanogenesis and melanosome transport still needs further study. In this research, we tried to further investigate how melanocyte melanogenesis is affected by pterostilbene and whether pterostilbene play a part in melanin transport. Our results showed that pterostilbene has a potent inhibitory effect on melanogenesis in B16F10 cells (3 μM, p < 0.001), in-vitro human skin (10 μM, p < 0.05) and zebrafish embryos (3 μM, p < 0.01). Besides, pterostilbene not only inhibited melanogenesis, but also inhibited melanocyte dendritic development and melanosome transport. Pterostilbene mainly plays a role by inhibiting cAMP/PKA/CREB signal pathway. After the cAMP/PKA/CREB signaling pathway was inhibited, tyrosinase activity and the expression of MITF, TYR, Rab27A, Rab17 and gp100 were decreased, which in turn suppressed melanogenesis, melanocyte dendritic development and melanosome transport. Our findings showed that pterostilbene can potently inhibit melanogenesis and melanosome transport, suggesting the applicability of pterostilbene in skin lightning. Therefore, a novel pharmacologic way to treat hyperpigmentation has been proposed.

Keywords: Melanocyte dendricity; Melanogenesis; Melanosome transport; Pterostilbene; cAMP/PKA/CREB signal Pathway.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / pharmacology
  • Cell Line, Tumor
  • Humans
  • Melanins*
  • Melanocytes
  • Melanosomes / metabolism
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Monophenol Monooxygenase / metabolism
  • Monophenol Monooxygenase / pharmacology
  • Stilbenes* / pharmacology
  • Zebrafish / metabolism

Substances

  • 3,5-dimethoxy-4'-hydroxystilbene
  • Anti-Inflammatory Agents
  • Antioxidants
  • Melanins
  • Microphthalmia-Associated Transcription Factor
  • Stilbenes
  • pterostilbene
  • Monophenol Monooxygenase