The Skin-Whitening Effects of Ectoine via the Suppression of α-MSH-Stimulated Melanogenesis and the Activation of Antioxidant Nrf2 Pathways in UVA-Irradiated Keratinocytes
Open Access
- 9 January 2020
- journal article
- research article
- Published by MDPI AG in Antioxidants
- Vol. 9 (1), 63
- https://doi.org/10.3390/antiox9010063
Abstract
Ultraviolet A (UVA)-irradiation induced reactive oxygen species (ROS) production mediates excessive melanogenesis in skin cells leading to pigmentation. We demonstrated the depigmenting and anti-melanogenic effects of Ectoine, a natural bacterial osmolyte, in UVA-irradiated human (HaCaT) keratinocytes, and the underlying molecular mechanisms were elucidated. HaCaT cells were pre-treated with low concentrations of Ectoine (0.5–1.5 μM) and assayed for various depigmenting and anti-melanogenic parameters. This pre-treatment significantly downregulated ROS generation, α-melanocyte-stimulating hormone (α-MSH) production, and proopiomelanocortin (POMC) expression in UVA-irradiated HaCaT cells. Also, antioxidant heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase [quinone 1] (NQO-1), and γ-glutamate-cysteine ligase catalytic subunit (γ-GCLC) protein expressions were mediated via the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) whose knockdown indeed impaired this effect signifying the importance of the Nrf2 pathway. Ectoine was mediating the activation of Nrf2 via the p38, protein kinase B (also known as AKT), protein kinase C (PKC), and casein kinase II protein kinase (CKII) pathways. The conditioned medium obtained from the Ectoine pre-treated and UVA-irradiated HaCaT cells downregulated the tyrosinase, tyrosinase-related protein-1 and -2 (TRP-1/-2), cyclic AMP (c-AMP) protein kinase, c-AMP response element-binding protein (CREB), and microphthalmia-associated transcription factor (MITF) expressions leading to melanoma B16F10 cells having inhibited melanin synthesis. Interestingly, this anti-melanogenic effect in α-MSH-stimulated B16F10 cells was observable only at 50–400 μM concentrations of Ectoine, signifying the key role played by Ectoine (0.5–1 μM)-treated keratinocytes in skin whitening effects. We concluded that Ectoine could be used as an effective topical natural cosmetic agent with depigmenting and anti-melanogenic efficacy.Keywords
Funding Information
- Ministry of Science and Technology, Taiwan (MOST-106-2320-B-039-054-MY3, MOST-107-2320-B-039-013-MY3)
- China Medical University, Taiwan (CMU 107-ASIA-15)
- Ministry of Education, Taiwan (CMRC-CHM-8)
This publication has 33 references indexed in Scilit:
- Ectoine-Containing Cream in the Treatment of Mild to Moderate Atopic Dermatitis: A Randomised, Comparator-Controlled, Intra-Individual Double-Blind, Multi-Center TrialSkin Pharmacology and Physiology, 2013
- Final Report of the Safety Assessment of Kojic Acid as Used in CosmeticsInternational Journal of Toxicology, 2010
- The effect of compatible solute ectoines on the structural organization of lipid monolayer and bilayer membranesBiophysical Chemistry, 2010
- The significance of Nrf2 pathway in (photo)‐oxidative stress response in melanocytes and keratinocytes of the human epidermisPigment Cell & Melanoma Research, 2008
- Skin lightening preparations and the hydroquinone controversyDermatologic Therapy, 2007
- Proopiomelanocortin (POMC), the ACTH/ melanocortin precursor, is secreted by human epidermal keratinocytes and melanocytes and stimulates melanogenesisThe FASEB Journal, 2007
- Ectoine and hydroxyectoine inhibit aggregation and neurotoxicity of Alzheimer's β‐amyloidFEBS Letters, 2005
- Allergic Contact Dermatitis Due to Kojic AcidDermatitis®, 2005
- Tetrahydropyrimidine derivatives inhibit binding of a Tat‐like, arginine‐containing peptide, to HIV TAR RNA in vitroFEBS Letters, 1995
- The biosynthesis of ectoineFEMS Microbiology Letters, 1990