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

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 ff-melanocytestimulating hormone (alpha-MSH) stimulation and without the alpha-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 alpha-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 alpha-MSH was added in the medium or not and the added time of the alpha-MSH. On this basis, the 100 mu g/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.

Automated summary

Epigallocatechin gallate (EGCG), gallocatechin gallate (GCG), theaflavine-3,3'-digallate (TFDG), and theasinensin A (TSA) effectively reduce melanin content and tyrosinase (TYR) activity without affecting cell viability. This study investigated their anti-melanogenic mechanisms and compared their activities at the molecular level. The results showed that these compounds downregulated key targets related to melanogenesis, including the melanocortin 1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), and the TYR family. Catechins had stronger downregulation abilities than dimers, and the compounds stably bound to the MC1R protein.