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      Jeju Magma-Seawater Inhibits α-MSH-Induced Melanogenesis via CaMKKβ-AMPK Signaling Pathways in B16F10 Melanoma Cells

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          Abstract

          Melanin protects skin from ultraviolet radiation, toxic drugs, and chemicals. Its synthesis is sophisticatedly regulated by multiple mechanisms, including transcriptional and enzymatic controls. However, uncontrolled excessive production of melanin can cause serious dermatological disorders, such as freckles, melasma, solar lentigo, and cancer. Moreover, melanogenesis disorders are also linked to neurodegenerative diseases. Therefore, there is a huge demand for safer and more potent inhibitors of melanogenesis. In the present study, we report novel inhibitory effects of Jeju magma-seawater (JMS) on melanogenesis induced by α-melanocyte stimulating hormone (α-MSH) in B16F10 melanoma cells. JMS is the abundant underground seawater found in Jeju Island, a volcanic island of Korea. Research into the physiological effects of JMS is rapidly increasing due to its high contents of various minerals that are essential to human health. However, little is known about the effects of JMS on melanogenesis. Here, we demonstrate that JMS safely and effectively inhibits α-MSH-induced melanogenesis via the CaMKKβ (calcium/calmodulin-dependent protein kinase β)-AMPK (5′ adenosine monophosphate-activated protein kinase) signaling pathway. We further demonstrate that AMPK inhibits the signaling pathways of protein kinase A and MAPKs (mitogen-activated protein kinase), which are critical for melanogenesis-related gene expression. Our results highlight the potential of JMS as a novel therapeutic agent for ameliorating skin pigmentation-related disorders.

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          Most cited references 49

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          The protective role of melanin against UV damage in human skin.

          Human skin is repeatedly exposed to UVR that influences the function and survival of many cell types and is regarded as the main causative factor in the induction of skin cancer. It has been traditionally believed that skin pigmentation is the most important photoprotective factor, as melanin, besides functioning as a broadband UV absorbent, has antioxidant and radical scavenging properties. Besides, many epidemiological studies have shown a lower incidence for skin cancer in individuals with darker skin compared to those with fair skin. Skin pigmentation is of great cultural and cosmetic importance, yet the role of melanin in photoprotection is still controversial. This article outlines the major acute and chronic effects of UVR on human skin, the properties of melanin, the regulation of pigmentation and its effect on skin cancer prevention.
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            Signaling Pathways in Melanogenesis

            Melanocytes are melanin-producing cells found in skin, hair follicles, eyes, inner ear, bones, heart and brain of humans. They arise from pluripotent neural crest cells and differentiate in response to a complex network of interacting regulatory pathways. Melanins are pigment molecules that are endogenously synthesized by melanocytes. The light absorption of melanin in skin and hair leads to photoreceptor shielding, thermoregulation, photoprotection, camouflage and display coloring. Melanins are also powerful cation chelators and may act as free radical sinks. Melanin formation is a product of complex biochemical events that starts from amino acid tyrosine and its metabolite, dopa. The types and amounts of melanin produced by melanocytes are determined genetically and are influenced by a variety of extrinsic and intrinsic factors such as hormonal changes, inflammation, age and exposure to UV light. These stimuli affect the different pathways in melanogenesis. In this review we will discuss the regulatory mechanisms involved in melanogenesis and explain how intrinsic and extrinsic factors regulate melanin production. We will also explain the regulatory roles of different proteins involved in melanogenesis.
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              Skin whitening agents: medicinal chemistry perspective of tyrosinase inhibitors

              Abstract Melanogenesis is a process to synthesize melanin, which is a primary responsible for the pigmentation of human skin, eye and hair. Although numerous enzymatic catalyzed and chemical reactions are involved in melanogenesis process, the enzymes such as tyrosinase and tyrosinase-related protein-1 (TRP-1) and TRP-2 played a major role in melanin synthesis. Specifically, tyrosinase is a key enzyme, which catalyzes a rate-limiting step of the melanin synthesis, and the downregulation of tyrosinase is the most prominent approach for the development of melanogenesis inhibitors. Therefore, numerous inhibitors that target tyrosinase have been developed in recent years. The review focuses on the recent discovery of tyrosinase inhibitors that are directly involved in the inhibition of tyrosinase catalytic activity and functionality from all sources, including laboratory synthetic methods, natural products, virtual screening and structure-based molecular docking studies.
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                Author and article information

                Journal
                Mar Drugs
                Mar Drugs
                marinedrugs
                Marine Drugs
                MDPI
                1660-3397
                18 September 2020
                September 2020
                : 18
                : 9
                Affiliations
                [1 ]Department of Biochemistry and Molecular Biology, Graduate School, College of Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea; thdalsgur77@ 123456khu.ac.kr (M.S.); hoang.dang.hieu.ls@ 123456gmail.com (D.H.H.); wchoe@ 123456khu.ac.kr (W.C.); iskang@ 123456khu.ac.kr (I.K.); sgskim@ 123456khu.ac.kr (S.S.K.)
                [2 ]Easy Hydrogen Corporation, Jeju City 63196, Korea; easyhydrogen@ 123456gmail.com
                [3 ]Department of Urology, College of Medicine, Jeju National University, Jeju City 63196, Korea; kurology@ 123456jejunu.ac.kr
                Author notes
                [* ]Correspondence: hajh@ 123456khu.ac.kr ; Tel.: +82-2-961-0287
                Article
                marinedrugs-18-00473
                10.3390/md18090473
                7551477
                32962063
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                Categories
                Article

                Pharmacology & Pharmaceutical medicine

                jeju magma-seawater, melanogenesis, ampk, pka, mapk

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