Miyake Masaki, Yamamoto Shigeto, Sano Osamu, Fujii Mitsukiyo, Kohno Keizo, Ushio Shimpei, Iwaki Kanso, Fukuda Shigeharu
Biomedical Institute, Research Center, Hayashibara Biochemical Laboratories, Inc., Okayama, Japan.
Biosci Biotechnol Biochem. 2010;74(4):753-8. doi: 10.1271/bbb.90795.
Hyperpigmentations are a serious concern addressed by both the medical community and the cosmetic industry through the development of agents that block melanin biosynthesis. In this study, we found that 2-amino-3H-phenoxazin-3-one (APO), isolated from extracts of the edible mushroom Agaricus bisporus Imbach, exhibited potent inhibitory effects on melanogenesis in B16 cells, a murine melanoma cell line. APO inhibited melanin biosynthesis at 1,000 times lower concentrations (IC(50)=1.31+/-0.08 microM) than kojic acid (IC(50)=1.31+/-0.13 mM), without causing cellular toxicity. APO did not directly inhibit the enzyme activity of tyrosinase, the rate-limiting melanogenic enzyme. Further study showed that APO inhibited the protein expression of tyrosinase and microphthalmia-associated transcription factor (MITF), a melanogenic transcription factor that regulates the expression of tyrosinase. These results suggest that APO is a promising depigmenting agent with both therapeutic and cosmetic value in preventing melanogenesis.
色素沉着过度是医学界和化妆品行业都非常关注的问题，为此研发了多种抑制黑色素生物合成的制剂。在本研究中，我们发现从双孢蘑菇（Agaricus bisporus Imbach）提取物中分离得到的2-氨基-3H-吩恶嗪-3-酮（APO）对小鼠黑色素瘤细胞系B16细胞的黑色素生成具有显著抑制作用。APO抑制黑色素生物合成的浓度（IC50 = 1.31±0.08 μM）比曲酸（IC50 = 1.31±0.13 mM）低1000倍，且不引起细胞毒性。APO不会直接抑制黑色素生成限速酶酪氨酸酶的酶活性。进一步研究表明，APO可抑制酪氨酸酶和小眼畸形相关转录因子（MITF，一种调节酪氨酸酶表达的黑色素生成转录因子）的蛋白表达。这些结果表明，APO是一种有前景的色素沉着抑制剂，在预防黑色素生成方面具有治疗和美容价值。
