Gallic acid (3, 4, 5‐trihydroxybenzoic acid) is a phytochemical derived from diverse herbs. It has been reported to have effective antifungal, antiviral and antioxidant activity. However, gallic acid exhibits low solubility and instability at high temperatures. In a previous study, in order to overcome these limitations, we synthesized galloyl‐RGD by combining gallic acid with arginine, glycine and asparaginic acid (RGD peptide). This compound showed better thermal stability than gallic acid. In this study, we investigated the antimelanogenic effect of galloyl‐RGD and the underlying mechanism for this effect. Galloyl‐RGD markedly inhibited melanin content and tyrosinase activity in a concentration‐dependent manner. We also found that galloyl‐RGD decreased the levels of melanogenesis‐related gene and protein. In addition, galloyl‐RGD reduces intracellular cyclic adenosine monophosphate (cAMP) levels that leads to inhibition of cAMP‐responsive element binding protein (CREB) phosphorylation and activates extracellular signal‐regulated kinase (ERK) expression. These results indicate that CREB and ERK regulation by galloyl‐RGD contributes to reduced melanin synthesis via degradation of microphthalmia‐associated transcription factor. Therefore, galloyl‐RGD can be potential candidate for application in cosmetic or pharmaceutical industry.

中文翻译：

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新合成的没食子酰-RGD 通过调节 B16F10 黑色素瘤细胞中的 CREB ​​和 ERK 信号通路抑制黑色素生成

没食子酸（3, 4, 5-三羟基苯甲酸）是一种来自多种草药的植物化学物质。据报道，它具有有效的抗真菌、抗病毒和抗氧化活性。然而，没食子酸在高温下表现出低溶解度和不稳定性。在之前的研究中，为了克服这些限制，我们通过将没食子酸与精氨酸、甘氨酸和天冬酰胺酸（RGD 肽）结合来合成没食子酰 RGD。该化合物显示出比没食子酸更好的热稳定性。在这项研究中，我们研究了没食子酰 RGD 的抗黑色素生成作用以及这种作用的潜在机制。Galloyl-RGD 以浓度依赖性方式显着抑制黑色素含量和酪氨酸酶活性。我们还发现没食子酰-RGD 降低了黑色素生成相关基因和蛋白质的水平。此外，没食子酰-RGD 降低细胞内环磷酸腺苷 (cAMP) 水平，从而抑制 cAMP 反应元件结合蛋白 (CREB) 磷酸化并激活细胞外信号调节激酶 (ERK) 表达。这些结果表明，没食子酰-RGD 对 CREB ​​和 ERK 的调节有助于通过降解小眼相关转录因子来减少黑色素合成。因此，没食子酰-RGD 可以成为化妆品或制药行业应用的潜在候选者。这些结果表明，没食子酰-RGD 对 CREB ​​和 ERK 的调节有助于通过降解小眼相关转录因子来减少黑色素合成。因此，没食子酰-RGD 可以成为化妆品或制药行业应用的潜在候选者。这些结果表明，没食子酰-RGD 对 CREB ​​和 ERK 的调节有助于通过降解小眼相关转录因子来减少黑色素合成。因此，没食子酰-RGD 可以成为化妆品或制药行业应用的潜在候选者。