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Melanins and Melanogenesis 4.0: From Nature to Applications

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 12376

Special Issue Editors


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Guest Editor
Department of Chemical Sciences, University of Naples “Federico II”, Via Cintia 4, I-80126 Naples, Italy
Interests: polyphenol antioxidants of dietary origin; conjugates of polyphenols with sulphydryl compounds of biological relevance; antioxidants from marine sources; valorization of agri food wastes; synthesis and exploitation of biopolymers from natural polyphenols; chemistry and structural investigation of natural polymers from catechols including human epidermal pigments melanins; oxidation chemistry of catecholamines in relation to neurodegenerative disorders; design and preparation of polydopamine related biomaterials with peculiar adhesive properties
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Guest Editor
Institute for Melanin Chemistry, Fujita Health University, Toyoake 470-1192, Japan
Interests: structure and properties of melanins; chemistry of melanogenesis; chemical analysis of melanins; effects of ultraviolet radiation and visible light on melanins; effects of heat on melanins; chemistry of tyrosinase-catalyzed oxidation of phenols
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Guest Editor
Department of Biology, University of Massachusetts Boston, 100 Morrissey Blvd, Boston, MA 02125, USA
Interests: enzymology; post translational modifications; aromatic metabolism; phenolic biochemistry; reactions of quinonoid compounds; invertebrate immunity; insect cuticular sclerotization; phenoloxidase; quinone isomerases; oxidative browning; melanin biosynthesis; catecholic antibiotics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Melanins are a vast class of biopolymers that are widespread in all types of organisms. They are responsible for the variety of skin, hair, and eye pigmentation in humans and other mammals, determine the colors of avian feathers, reptiles, amphibians, fishes, and insects, but largely occur also in lower organisms such as fungi and bacteria.

In humans, two main types of melanins are found, the black insoluble eumelanin, characterizing dark phenotypes; and the reddish-brown, sulfur-containing pheomelanin, typical of red-haired individuals. In addition, substantia nigra neuromelanin and extracutaneous melanins of the inner ear and iridial epithelium are known. Both eumelanins and pheomelanins are produced within melanocytes by a complex biosynthetic pathway involving the tyrosinase-catalyzed oxidation of tyrosine.

Many factors, either enzymatic or not, intervene in the melanogenic pathway, ultimately determining the eumelanin and pheomelanin pigmentation. Dysregulation of these control mechanisms results in a variety of pigmentary disorders, from melasma to vitiligo, bearing severe pathological implications and often dramatic aesthetic impacts.

Intense research work over the past few decades has disclosed a variety of roles for melanin pigments, from photoprotection to photosensitization, from antioxidant defense to metal/drug binding. Neuromelanin is believed to be involved in neurodegeneration, and to be related to Parkinson's disease.

However, we have yet to fully appreciate how these peculiar properties of melanin pigments and how the tuning of melanogenesis could be exploited for developing strategies for the control of melanin disorders, photoprotection, the implementation of all-natural or bioinspired antioxidants, metal detoxification, ingredients for cosmetic or dermocosmetic uses.

This Special Issue takes advantage of the open-access format to offer a novel and stimulating perspective of the field. It is especially directed to translate the results of basic and academic research to applications that may arouse the interest of researchers from industries and companies who are willing to develop innovative melanin- or melanogenesis-based solutions.

Contributions to this Special Issue may cover all aspects of the chemistry of natural and synthetic melanins with potential applications, melanogenesis inhibitors via the definition of the mechanism of action, approaches for the amelioration or control of all types of melanin-based pigmentary disorders, and photoprotection strategies; innovative methodologies for the analysis of pigmented tissues and for diagnostic purposes; molecular engineering methodologies for melanin production in microorganisms; and novel functions of melanins of potential application interest, drug targeting, and exploiting the specific affinity of melanins.

Experimental papers, up-to-date review articles, and commentaries are all welcome.

Prof. Dr. Alessandra Napolitano
Prof. Dr. Shosuke Ito
Prof. Dr. Manickam Sugumaran
Guest Editors

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Keywords

  • eumelanin
  • photoprotection
  • biological activities
  • antioxidant
  • depigmenting agents
  • melanogenesis
  • dermocosmetics
  • pigmentary disorders
  • pheomelanin
  • extracutaneous melanins

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Published Papers (5 papers)

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Research

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17 pages, 6207 KiB  
Article
Discovery of Kuraridin as a Potential Natural Anti-Melanogenic Agent: Focusing on Specific Target Genes and Multidirectional Signaling Pathways
by Subin Jeon, Kumju Youn and Mira Jun
Int. J. Mol. Sci. 2024, 25(20), 11227; https://doi.org/10.3390/ijms252011227 - 18 Oct 2024
Viewed by 708
Abstract
Abnormal melanogenesis upon UV exposure causes excessive oxidative stress, leading to hyperpigmentation disorders. As a key rate-limiting enzyme in melanogenesis, tyrosinase is considered a primary target for depigmenting agents. Sophora flavescens is used as a food and in traditional medicine as a valuable [...] Read more.
Abnormal melanogenesis upon UV exposure causes excessive oxidative stress, leading to hyperpigmentation disorders. As a key rate-limiting enzyme in melanogenesis, tyrosinase is considered a primary target for depigmenting agents. Sophora flavescens is used as a food and in traditional medicine as a valuable source of prenylated flavonoids. The present study aimed to elucidate the anti-melanogenic effect and potential mechanism of kuraridin, one of the major prenylated flavonoids. Kuraridin showed anti-tyrosinase activity with an IC50 value in the nanomolar range, superior to that of kojic acid, a positive control. It significantly reduced tyrosinase activity with the least cytotoxicity, suppressing melanogenesis in α-MSH-induced B16F10 cells. Furthermore, kuraridin considerably reduced melanogenesis in a 3D human skin model. To elucidate the anti-melanogenic mechanism of kuraridin, target genes (KIT, MAP2K1, and PRKCA) and pathways (c-KIT and ETB-R pathways) were identified using network pharmacology. KIT and MAP2K1 are simultaneously involved in the c-KIT cascade and are considered the most important in melanogenesis. PRKCA acts directly on MITF and its downstream enzymes through another pathway. Docking simulation showed strong interactions between kuraridin and c-KIT, ERK1/2, and PKC encoded by target genes. Overall, the present study showed kuraridin to be a novel natural anti-melanogenic agent in hyperpigmentation disorders. Full article
(This article belongs to the Special Issue Melanins and Melanogenesis 4.0: From Nature to Applications)
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15 pages, 2477 KiB  
Article
Exploring the Influence of Cold Plasma on Epidermal Melanogenesis In Situ and In Vitro
by Sybille Hasse, Marie-Christine Sommer, Sebastian Guenther, Christian Schulze, Sander Bekeschus and Thomas von Woedtke
Int. J. Mol. Sci. 2024, 25(10), 5186; https://doi.org/10.3390/ijms25105186 - 10 May 2024
Viewed by 1224
Abstract
Epidermal melanin synthesis determines an individual’s skin color. In humans, melanin is formed by melanocytes within the epidermis. The process of melanin synthesis strongly depends on a range of cellular factors, including the fine-tuned interplay with reactive oxygen species (ROS). In this context, [...] Read more.
Epidermal melanin synthesis determines an individual’s skin color. In humans, melanin is formed by melanocytes within the epidermis. The process of melanin synthesis strongly depends on a range of cellular factors, including the fine-tuned interplay with reactive oxygen species (ROS). In this context, a role of cold atmospheric plasma (CAP) on melanin synthesis was proposed due to its tunable ROS generation. Herein, the argon-driven plasma jet kINPen® MED was employed, and its impact on melanin synthesis was evaluated by comparison with known stimulants such as the phosphodiesterase inhibitor IBMX and UV radiation. Different available model systems were employed, and the melanin content of both cultured human melanocytes (in vitro) and full-thickness human skin biopsies (in situ) were analyzed. A histochemical method detected melanin in skin tissue. Cellular melanin was measured by NIR autofluorescence using flow cytometry, and a highly sensitive HPLC-MS method was applied, which enabled the differentiation of eu- and pheomelanin by their degradation products. The melanin content in full-thickness human skin biopsies increased after repeated CAP exposure, while there were only minor effects in cultured melanocytes compared to UV radiation and IBMX treatment. Based on these findings, CAP does not appear to be a useful option for treating skin pigmentation disorders. On the other hand, the risk of hyperpigmentation as an adverse effect of CAP application for wound healing or other dermatological diseases seems to be neglectable. Full article
(This article belongs to the Special Issue Melanins and Melanogenesis 4.0: From Nature to Applications)
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16 pages, 3090 KiB  
Article
Eumelanin Detection in Melanized Focal Changes but Not in Red Focal Changes on Atlantic Salmon (Salmo salar) Fillets
by Kazumasa Wakamatsu, Johannes M. Dijkstra, Turid Mørkøre and Shosuke Ito
Int. J. Mol. Sci. 2023, 24(23), 16797; https://doi.org/10.3390/ijms242316797 - 27 Nov 2023
Cited by 2 | Viewed by 2817
Abstract
Superficial discolored spots on Atlantic salmon (Salmo salar) fillets are a serious quality problem for commercial seafood farming. Previous reports have proposed that the black spots (called melanized focal changes (MFCs)) may be melanin, but no convincing evidence has been reported. [...] Read more.
Superficial discolored spots on Atlantic salmon (Salmo salar) fillets are a serious quality problem for commercial seafood farming. Previous reports have proposed that the black spots (called melanized focal changes (MFCs)) may be melanin, but no convincing evidence has been reported. In this study, we performed chemical characterization of MFCs and of red pigment (called red focal changes (RFCs)) from salmon fillets using alkaline hydrogen peroxide oxidation and hydroiodic acid hydrolysis. This revealed that the MFCs contain 3,4-dihydroxyphenylalanine (DOPA)-derived eumelanin, whereas the RFCs contain only trace amounts of eumelanin. Therefore, it is probable that the black color of the MFCs can be explained by the presence of eumelanin from accumulated melanomacrophages. For the red pigment, we could not find a significant signature of either eumelanin or pheomelanin; the red color is probably predominantly hemorrhagic in nature. However, we found that the level of pigmentation in RFCs increased together with some melanogenic metabolites. Comparison with a “mimicking experiment”, in which a mixture of a salmon homogenate + DOPA was oxidized with tyrosinase, suggested that the RFCs include conjugations of DOPAquinone and/or DOPAchrome with salmon muscle tissue proteins. In short, the results suggest that melanogenic metabolites in MFCs and RFCs derive from different chemical pathways, which would agree with the two different colorations deriving from distinct cellular origins, namely melanomacrophages and red blood cells, respectively. Full article
(This article belongs to the Special Issue Melanins and Melanogenesis 4.0: From Nature to Applications)
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Review

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14 pages, 964 KiB  
Review
Role of Dermal Factors Involved in Regulating the Melanin and Melanogenesis of Mammalian Melanocytes in Normal and Abnormal Skin
by Tomohisa Hirobe
Int. J. Mol. Sci. 2024, 25(8), 4560; https://doi.org/10.3390/ijms25084560 - 22 Apr 2024
Viewed by 1425
Abstract
Mammalian melanin is produced in melanocytes and accumulated in melanosomes. Melanogenesis is supported by many factors derived from the surrounding tissue environment, such as the epidermis, dermis, and subcutaneous tissue, in addition to numerous melanogenesis-related genes. The roles of these genes have been [...] Read more.
Mammalian melanin is produced in melanocytes and accumulated in melanosomes. Melanogenesis is supported by many factors derived from the surrounding tissue environment, such as the epidermis, dermis, and subcutaneous tissue, in addition to numerous melanogenesis-related genes. The roles of these genes have been fully investigated and the molecular analysis has been performed. Moreover, the role of paracrine factors derived from epidermis has also been studied. However, the role of dermis has not been fully studied. Thus, in this review, dermis-derived factors including soluble and insoluble components were overviewed and discussed in normal and abnormal circumstances. Dermal factors play an important role in the regulation of melanogenesis in the normal and abnormal mammalian skin. Full article
(This article belongs to the Special Issue Melanins and Melanogenesis 4.0: From Nature to Applications)
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32 pages, 3085 KiB  
Review
Recent Advances in Characterization of Melanin Pigments in Biological Samples
by Kazumasa Wakamatsu and Shosuke Ito
Int. J. Mol. Sci. 2023, 24(9), 8305; https://doi.org/10.3390/ijms24098305 - 5 May 2023
Cited by 15 | Viewed by 5501
Abstract
The melanin pigments eumelanin (EM) and pheomelanin (PM), which are dark brown to black and yellow to reddish-brown, respectively, are widely found among vertebrates. They are produced in melanocytes in the epidermis, hair follicles, the choroid, the iris, the inner ear, and other [...] Read more.
The melanin pigments eumelanin (EM) and pheomelanin (PM), which are dark brown to black and yellow to reddish-brown, respectively, are widely found among vertebrates. They are produced in melanocytes in the epidermis, hair follicles, the choroid, the iris, the inner ear, and other tissues. The diversity of colors in animals is mainly caused by the quantity and quality of their melanin, such as by the ratios of EM versus PM. We have developed micro-analytical methods to simultaneously measure EM and PM and used these to study the biochemical and genetic fundamentals of pigmentation. The photoreactivity of melanin has become a major focus of research because of the postulated relevance of EM and PM for the risk of UVA-induced melanoma. Our biochemical methods have found application in many clinical studies on genetic conditions associated with alterations in pigmentation. Recently, besides chemical degradative methods, other methods have been developed for the characterization of melanin, and these are also discussed here. Full article
(This article belongs to the Special Issue Melanins and Melanogenesis 4.0: From Nature to Applications)
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