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,Jing-Yuan Chuang,Hung-Rong Yen,Hsin-Ling Yang,Yugandhar Vudhya Gowrisankar

doi:10.3390/antiox9010063

You-Cheng Hseu, Xuan-Zao Chen + Show 4 more

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https://doi.org/10.3390/antiox9010063

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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.

Highlights

Exposing human skin to Ultraviolet A (UVA) radiation triggers reactive oxygen species (ROS) generation and over-producing melanin in the skin cells
We concluded that low concentrations of Ectoine (0.5–1.5 μM) could downregulate α-melanocyte-stimulating hormone (α-MSH) and melanin production via the suppression of POMC and tyrosinase pathway in UVA irradiated HaCaT cells, indicating its anti-melanogenesis efficacy
Unlike HaCaT cells, high concentrations of Ectoine (50–400 μM) were able to show the similar effect in B16F10 melanoma cells that have signified the fact that keratinocytes could play a key role in the Ectoine mediated anti-melanogenesis and skin-whitening effects in skin cells

Summary

Introduction

Exposing human skin to UVA radiation triggers ROS generation and over-producing melanin in the skin cells. Skin whitening agents from the natural sources, for example, Kojic acid (a fungal derivative obtained from Penicillium and Aspergillus species) is reported to cause ‘contact dermatitis’ in individuals who have sensitive skin. In these individuals, more than 1% of kojic acid could cause severe hypersensitive side effects [4,5]. The skincare products that are principally targeting the depigmenting properties have at times failed to focus on counteracting the deleterious effects posed by the UVA irradiation-induced ROS production mediated excess melanogenesis in skin cells

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