The in vitro and in vivo depigmenting activity of Coenzyme Q10 through the down-regulation of α-MSH signaling pathways and induction of Nrf2/ARE-mediated antioxidant genes in UVA-irradiated skin keratinocytes

Biochem Pharmacol. 2019 Jun:164:299-310. doi: 10.1016/j.bcp.2019.04.015. Epub 2019 Apr 13.

Abstract

Coenzyme CoQ10 (CoQ10), a ubiquinone compound, has been reported to inhibit tyrosinase activity and melanin production in melanoma B16F10 cells. However, the molecular mechanism underlying this inhibitory effect is poorly understood. In this paper we aimed to investigate the molecular mechanisms involved in the anti-melanogenic activity of CoQ10 (1-2 μM) in UVA (5 J/cm2)-irradiated keratinocyte HaCaT cells and α-MSH stimulated B16-F10 cells. It was observed that CoQ10 suppressed p53/POMC, α-MSH production as well as inhibited ROS generation in UVA-irradiated keratinocyte HaCaT cells. CoQ10 down-regulated the melanin synthesis in α-MSH-stimulated B16-F10 cells by suppressing the MITF expression by down regulating the cAMP mediated CREB signaling cascades. Furthermore, in vivo evidence demonstrated the inhibitory effect of CoQ10 on endogenous pigmentation in zebrafish. Increased nuclear Nrf2 translocation accompanied by the induction of HO-1 and γ-GCLC genes were observed in CoQ10 treated keratinocyte HaCaT cells. Notably, silencing of Nrf2 (siRNA transfection) significantly diminished CoQ10-mediated anti-melanogenic activity, as evidenced by impaired antioxidant HO-1 gene, uncontrolled ROS generation, and α-MSH production following UVA irradiation. To conclude, CoQ10 is an effective de-pigmention or skin-whitening agent and could be used in cosmetics for topical application.

Keywords: CoQ10; Nrf2; UVA; Zebrafish; α-MSH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Carboxylic Ester Hydrolases / biosynthesis*
  • Carboxylic Ester Hydrolases / genetics
  • Cell Line, Transformed
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism*
  • Keratinocytes / radiation effects
  • Melanoma, Experimental / metabolism
  • Mice
  • NF-E2-Related Factor 2 / biosynthesis*
  • NF-E2-Related Factor 2 / genetics
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Skin / drug effects
  • Skin / metabolism
  • Skin / radiation effects
  • Skin Lightening Preparations / pharmacology*
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / pharmacology
  • Ultraviolet Rays*
  • Zebrafish
  • alpha-MSH / antagonists & inhibitors
  • alpha-MSH / metabolism*

Substances

  • Antioxidants
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Skin Lightening Preparations
  • Ubiquinone
  • alpha-MSH
  • Carboxylic Ester Hydrolases
  • arylesterase
  • coenzyme Q10