Sato Kazuomi, Takahashi Hideki, Iraha Remina, Toriyama Masaru
United Graduate School of Agricultural Science, Gifu University, Yanagido, Gifu 501-1193, Japan.
Biol Pharm Bull. 2008 Jan;31(1):33-7. doi: 10.1248/bpb.31.33.
Acetylsalicylic acid (aspirin; ASA) is widely used as an analgesic/antipyretic drug. ASA exhibits a wide range of biological effects, including preventative effects against heart attack, stroke, and the development of some types of cancer. However, the effects of ASA on melanogenesis are not well known. Therefore, we investigated the effect of ASA on melanin production using B16 murine melanoma cells and demonstrated a new biological effect of ASA. In the presence of alpha-melanocyte stimulating hormone (alpha-MSH), B16 melanoma cells are stimulated to enhance melanin synthesis. ASA (2 mM) inhibited alpha-MSH-enhanced melanin synthesis in melanoma more strongly than other well-known anti-melanogenic agents such as arbutin (2 mM) and kojic acid (200 microM). Interestingly, ASA did not inhibit the catalytic activity of mushroom tyrosinase (concentration range 0.5-4.0 mM). To clarify the target of ASA action in melanogenesis, we performed Western blotting for tyrosinase, which is a key melanogenic enzyme. ASA inhibited tyrosinase expression in a dose-dependent manner. Therefore, the depigmenting effect of ASA might be due to inhibition of tyrosinase expression or enhancement of tyrosinase degradation. This study suggests that ASA is a candidate anti-melanogenic agent and it might be effective in hyperpigmentation disorders.
乙酰水杨酸（阿司匹林；ASA）作为一种镇痛/解热药物被广泛使用。ASA具有广泛的生物学效应，包括对心脏病发作、中风以及某些类型癌症发展的预防作用。然而，ASA对黑色素生成的影响尚不清楚。因此，我们使用B16小鼠黑色素瘤细胞研究了ASA对黑色素生成的影响，并证明了ASA的一种新的生物学效应。在α-黑素细胞刺激素（α-MSH）存在的情况下，B16黑色素瘤细胞被刺激以增强黑色素合成。与其他知名的抗黑色素生成剂如熊果苷（2 mM）和曲酸（200 microM）相比，ASA（2 mM）更强烈地抑制了黑色素瘤中α-MSH增强的黑色素合成。有趣的是，ASA没有抑制蘑菇酪氨酸酶的催化活性（浓度范围为0.5-4.0 mM）。为了阐明ASA在黑色素生成中的作用靶点，我们对黑色素生成关键酶酪氨酸酶进行了蛋白质印迹分析。ASA以剂量依赖性方式抑制酪氨酸酶表达。因此，ASA的色素脱失作用可能是由于抑制酪氨酸酶表达或增强酪氨酸酶降解。本研究表明，ASA是一种潜在的抗黑色素生成剂，可能对色素沉着过度症有效。
