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      Natural skin-whitening compounds for the treatment of melanogenesis (Review)

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          Abstract

          Melanogenesis is the process for the production of melanin, which is the primary cause of human skin pigmentation. Skin-whitening agents are commercially available for those who wish to have a lighter skin complexions. To date, although numerous natural compounds have been proposed to alleviate hyperpigmentation, insufficient attention has been focused on potential natural skin-whitening agents and their mechanism of action from the perspective of compound classification. In the present article, the synthetic process of melanogenesis and associated core signaling pathways are summarized. An overview of the list of natural skin-lightening agents, along with their compound classifications, is also presented, where their efficacy based on their respective mechanisms of action on melanogenesis is discussed.

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          Human skin pigmentation: melanocytes modulate skin color in response to stress.

          Gertrude-E Costin, Vincent J. Hearing (2007)
          All organisms, from simple invertebrates to complex human beings, exist in different colors and patterns, which arise from the unique distribution of pigments throughout the body. Pigmentation is highly heritable, being regulated by genetic, environmental, and endocrine factors that modulate the amount, type, and distribution of melanins in the skin, hair, and eyes. In addition to its roles in camouflage, heat regulation, and cosmetic variation, melanin protects against UV radiation and thus is an important defense system in human skin against harmful factors. Being the largest organ of the body that is always under the influence of internal and external factors, the skin often reacts to those agents by modifying the constitutive pigmentation pattern. The focus of this review is to provide an updated overview of important physiological and biological factors that increase pigmentation and the mechanisms by which they do so. We consider endocrine factors that induce temporary (e.g., during pregnancy) or permanent (e.g., during aging) changes in skin color, environmental factors (e.g., UV), certain drugs, and chemical compounds, etc. Understanding the mechanisms by which different factors and compounds induce melanogenesis is of great interest pharmaceutically (as therapy for pigmentary diseases) and cosmeceutically (e.g., to design tanning products with potential to reduce skin cancer risk).
          Article 0 comments Cited 234 times – based on 0 reviews     Review now
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            Melanocytes and the microphthalmia transcription factor network.

            Eirikur Steingrimsson, Neal Copeland, Nancy A. Jenkins (2004)
            The first mouse microphthalmia transcription factor (Mitf ) mutation was discovered over 60 years ago, and since then over 24 spontaneous and induced mutations have been identified at the locus. Mitf encodes a member of the Myc supergene family of basic helix-loop-helix zipper (bHLH-Zip) transcription factors. Like Myc, Mitf regulates gene expression by binding to DNA as a homodimer or as a heterodimer with another related family member, in the case of Mitf the Tfe3, Tfeb, and Tfec proteins. The study of Mitf has provided many insights into the biology of melanocytes and helped to explain how melanocyte-specific gene expression and signaling is regulated. The human homologue of MITF is mutated in patients with the pigmentary and deafness disorder Waardenburg Syndrome Type 2A (WS2A). The mouse Mitf mutations therefore serve as a model for the study of this human disease. Mutations and/or aberrant expression of several MITF family member genes have also been reported in human cancer, including melanoma (MITF), papillary renal cell carcinoma (TFE3, TFEB), and alveolar soft part sarcoma (TFE3). Genes in the MITF/TFE pathway may therefore also represent valuable therapeutic targets for the treatment of human cancer. Here we review recent developments in the analysis of Mitf function in vivo and in vitro and show how traditional genetics, modern forward genetics and in vitro biochemical analyses have combined to produce an intriguing story on the role and actions of a gene family in a living organism.
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              Hypopigmenting agents: an updated review on biological, chemical and clinical aspects.

              Stefania Briganti, Mauro Picardo, Mauro Picardo … (2006)
              An overview of agents causing hypopigmentation in human skin is presented. The review is organized to put forward groups of biological and chemical agents. Their mechanisms of action cover (i) tyrosinase inhibition, maturation and enhancement of its degradation; (ii) Mitf inhibition; (iii) downregulation of MC1R activity; (iv) interference with melanosome maturation and transfer; (v) melanocyte loss, desquamation and chemical peeling. Tyrosinase inhibition is the most common approach to achieve skin hypopigmentation as this enzyme catalyses the rate-limiting step of pigmentation. Despite the large number of tyrosinase inhibitors in vitro, only a few are able to induce effects in clinical trials. The gap between in-vitro and in-vivo studies suggests that innovative strategies are needed for validating their efficacy and safety. Successful treatments need the combination of two or more agents acting on different mechanisms to achieve a synergistic effect. In addition to tyrosinase inhibition, other parameters related to cytotoxicity, solubility, cutaneous absorption, penetration and stability of the agents should be considered. The screening test system is also very important as keratinocytes play an active role in modulating melanogenesis within melanocytes. Mammalian skin or at least keratinocytes/melanocytes co-cultures should be preferred rather than pure melanocyte cultures or soluble tyrosinase.
              Article 0 comments Cited 153 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Exp Ther Med
                Journal ID (iso-abbrev): Exp Ther Med
                Journal ID (publisher-id): ETM
                Title: Experimental and Therapeutic Medicine
                Publisher: D.A. Spandidos
                ISSN (Print): 1792-0981
                ISSN (Electronic): 1792-1015
                Publication date (Print): July 2020
                Publication date (Electronic): 24 April 2020
                Publication date PMC-release: 24 April 2020
                Volume: 20
                Issue: 1
                Pages: 173-185
                Affiliations
                [1 ]Department of Pharmaceutics, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China
                [2 ]School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210002, P.R. China
                Author notes
                Correspondence to: Dr Guangming Gong or Mrs. Hua Su, Department of Pharmaceutics, Jinling Hospital, Nanjing University School of Medicine, 305 Zhongshan Road, Nanjing, Jiangsu 210002, P.R. China gonggm@ 123456126.com suhuash@ 123456sina.com
                Article
                Publisher ID: ETM-0-0-8687
                DOI: 10.3892/etm.2020.8687
                PMC ID: 7271691
                PubMed ID: 32509007
                SO-VID: 93eac160-65b9-462f-8d34-b99a685225d1
                Copyright © Copyright: © Qian et al.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                Date received : 14 June 2019
                Date accepted : 17 March 2020
                Categories
                Subject: Review

                ScienceOpen disciplines: Medicine
                Keywords: melanogenesis,skin-whitening agents,natural sources,tyrosinase
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: melanogenesis, skin-whitening agents, natural sources, tyrosinase

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