EGCG, GCG, TFDG, or TSA Inhibiting Melanin Synthesis by Downregulating MC1R Expression.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Melanins*/metabolism ; Melanoma, Experimental*; Animals ; alpha-MSH/pharmacology ; alpha-MSH/metabolism ; Receptor, Melanocortin, Type 1/genetics ; Monophenol Monooxygenase/metabolism ; Molecular Docking Simulation ; Microphthalmia-Associated Transcription Factor/genetics ; Microphthalmia-Associated Transcription Factor/metabolism ; Cell Line, Tumor

Without affecting cell viability, epigallocatechin gallate (EGCG), gallocatechin gallate (GCG), theaflavine-3,3'-digallate (TFDG), or theasinensin A (TSA) have been found to effectively reduce intracellular melanin content and tyrosinase (TYR) activity. However, studies on the anti-melanogenic mechanism of the above samples remain weak, and the activities of these samples in regulating melanogenesis at the molecular level lack comparison. Using B16F10 cells with the α-melanocyte-stimulating hormone (α-MSH) stimulation and without the α-MSH stimulation as models, the effects of EGCG, GCG, TFDG, or TSA on cell phenotypes and expression of key targets related to melanogenesis were studied. The results showed that α-MSH always promoted melanogenesis with or without adding the four samples. Meanwhile, the anti-melanogenic activities of the four samples were not affected by whether the α-MSH was added in the medium or not and the added time of the α-MSH. On this basis, the 100 µg/mL EGCG, GCG, TFDG, or TSA did not affect the TYR catalytic activity but inhibited melanin formation partly through downregulating the melanocortin 1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), and the TYR family. The downregulation abilities of catechins on the TYR family and MITF expression were stronger than those of dimers at both the transcription and translation levels, while the ability of dimers to downregulate the MC1R expression was stronger than that of catechins at both the transcription and translation levels to some extent. The results of molecular docking showed that these four samples could stably bind to MC1R protein. Taken together, this study offered molecular mechanisms for the anti-melanogenic activity of the EGCG, GCG, TFDG, and TSA, as potential effective components against the UV-induced tanning reactions, and a key target (MC1R) was identified.

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31670692 National Natural Science Foundation of China; Y2021GH06 Basic Scientific Research Project of Chinese Academy of Agricultural Sciences; CAAS-ASTIP-2023-TRICAAS Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences

Keywords: MC1R; TYR; catechins and their dimers; melanin; α-MSH

0 (Melanins)
581-05-5 (alpha-MSH)
0 (Receptor, Melanocortin, Type 1)
BQM438CTEL (epigallocatechin gallate)
EC 1.14.18.1 (Monophenol Monooxygenase)
0C056HB16M (gallocatechin gallate)
0 (Microphthalmia-Associated Transcription Factor)

Date Created: 20230714 Date Completed: 20230717 Latest Revision: 20230718

20231215

PMC10341940

10.3390/ijms241311017

37446194