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

You-Cheng Hseu; Xuan-Zao Chen; Yugandhar Vudhya Gowrisankar; Hung-Rong Yen; Jing-Yuan Chuang; Hsin-Ling Yang

doi:10.3390/antiox9010063

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

Antioxidants (Basel). 2020 Jan 10;9(1):63. doi: 10.3390/antiox9010063.

Authors

You-Cheng Hseu^{1

2

3

4}, Xuan-Zao Chen¹, Yugandhar Vudhya Gowrisankar¹, Hung-Rong Yen^{3

4

5

6}, Jing-Yuan Chuang⁷, Hsin-Ling Yang⁸

Affiliations

¹ Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan.
² Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan.
³ Chinese Medicine Research Center, China Medical University, Taichung 40402, Taiwan.
⁴ Research Center of Chinese Herbal Medicine, China Medical University, Taichung 40402, Taiwan.
⁵ Department of Medical Research, China Medical University Hospital, Taichung 40402, Taiwan.
⁶ School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
⁷ Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan.
⁸ Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, 91 Hsueh-Shih Road, Taichung 40402, Taiwan.

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: Ectoine; Nrf2; keratinocytes; melanogenesis; tyrosinase; α-MSH.

Abstract

Grants and funding