Antai Medical Care Cooperation Antai Tian-Sheng Memorial Hospital, Pingtung 92842, Taiwan.
Int J Mol Sci. 2013 Oct 14;14(10):20443-58. doi: 10.3390/ijms141020443.
Gallic acid is one of the major flavonoids found in plants. It acts as an antioxidant, and seems to have anti-inflammatory, anti-viral, and anti-cancer properties. In this study, we investigated the effects of gallic acid on melanogenesis, including the activation of melanogenesis signaling pathways. Gallic acid significantly inhibited both melanin synthesis and tyrosinase activity in a dose- and time-dependent manner, and decreased the expression of melanogenesis-related proteins, such as microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), and dopachrome tautomerase (Dct). In addition, gallic acid also acts by phosphorylating and activating melanogenesis inhibitory proteins such as Akt and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK). Using inhibitors against PI3K/Akt (LY294002) or MEK/ERK-specific (PD98059), the hypopigmentation effect was suppressed, and the gallic acid-initiated activation of MEK/ERK and PI3K/Akt was also revoked. Gallic acid also increased GSK3β and p-β-catenin expression but down-regulated p-GSK3β. Moreover, GSK3β-specific inhibitor (SB216763) restored gallic acid-induced melanin reduction. These results suggest that activation of the MEK/ERK, PI3K/Akt, and inhibition of Wnt/β-catenin signaling pathways is involved in the melanogenesis signaling cascade, and that activation by gallic acid reduces melanin synthesis via down-regulation of MITF and its downstream signaling pathway. In conclusion, gallic acid may be a potentially agent for the treatment of certain skin conditions.
没食子酸是植物中主要的类黄酮之一。它具有抗氧化作用，似乎具有抗炎、抗病毒和抗癌特性。在这项研究中，我们研究了没食子酸对黑色素生成的影响，包括对黑色素生成信号通路的激活。没食子酸以剂量和时间依赖的方式显著抑制黑色素合成和酪氨酸酶活性，并降低黑色素生成相关蛋白的表达，如小眼畸形相关转录因子（MITF）、酪氨酸酶、酪氨酸酶相关蛋白-1（TRP1）和多巴色素互变异构酶（Dct）。此外，没食子酸还通过磷酸化和激活黑色素生成抑制蛋白如 Akt 和丝裂原活化蛋白激酶（MEK）/细胞外信号调节激酶（ERK）起作用。使用针对 PI3K/Akt（LY294002）或 MEK/ERK 特异性（PD98059）的抑制剂，抑制了色素减退作用，并且撤销了没食子酸引发的 MEK/ERK 和 PI3K/Akt 的激活。没食子酸还增加了 GSK3β 和 p-β-catenin 的表达，但下调了 p-GSK3β。此外，GSK3β 特异性抑制剂（SB216763）恢复了没食子酸诱导的黑色素减少。这些结果表明，MEK/ERK、PI3K/Akt 的激活和 Wnt/β-catenin 信号通路的抑制参与了黑色素生成信号级联，而没食子酸的激活通过下调 MITF 及其下游信号通路来减少黑色素合成。总之，没食子酸可能是治疗某些皮肤疾病的潜在药物。
