Department of Molecular Medicine and Cell and Matrix Research Institute, BK21 Medical Education Program for Human Resources, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
Phytother Res. 2010 Aug;24(8):1175-80. doi: 10.1002/ptr.3095.
Tyrosinase (TYR) catalyzes rate-limiting steps of melanogenesis and thus its inhibitors are potentially useful as hypopigmenting agents. Recently, p-coumaric acid (p-CA) has been suggested to interfere with the pro-melanogenic actions of tyrosine due to its structural similarity with tyrosine (An SM et al., Br J Dermatol 2008. 159: 292). In this study, we compared the inhibitory effects of p-CA and two other well known TYR inhibitors used in cosmetics--arbutin and kojic acid--on the catalytic activities of mushroom, murine and human TYRs in vitro, using tyrosine and 3,4-dihydroxyphenylalanine (DOPA) as substrates. The results showed that p-CA is a weaker inhibitor of mushroom TYR but much stronger inhibitor of human or murine TYR in comparison with kojic acid and arbutin. In addition, p-CA inhibited human TYR at much lower concentrations than those required for the inhibition of murine or mushroom TYRs. Enzyme kinetics analysis indicated that p-CA is a mixed type (for tyrosine) or competitive inhibitor (for DOPA) of human TYR. Potent antimelanogenic effects of p-CA were observed in human epidermal melanocytes exposed to UVB. The present study demonstrated that p-CA is a potent and selective inhibitor of human TYR and is potentially useful as a hypopigmenting agent.
酪氨酸酶（TYR）催化黑色素生成的限速步骤，因此其抑制剂可能作为减色剂具有潜在的用途。最近，由于结构上与酪氨酸相似，对肉桂酸（p-CA）被认为可以干扰酪氨酸的促黑色素生成作用（An SM 等人，Br J Dermatol 2008. 159: 292）。在这项研究中，我们比较了 p-CA 与两种常用于化妆品的其他酪氨酸酶抑制剂——熊果苷和曲酸——对蘑菇、鼠和人酪氨酸酶在体外对酪氨酸和 3,4-二羟苯丙氨酸（DOPA）的催化活性的抑制作用。结果表明，与曲酸和熊果苷相比，p-CA 是蘑菇酪氨酸酶较弱的抑制剂，但对人或鼠酪氨酸酶的抑制作用要强得多。此外，p-CA 抑制人酪氨酸酶所需的浓度比抑制鼠或蘑菇酪氨酸酶低得多。酶动力学分析表明，p-CA 是人酪氨酸酶的混合（对酪氨酸）或竞争性抑制剂（对 DOPA）。p-CA 对暴露于 UVB 的人表皮黑素细胞具有很强的抗黑色素生成作用。本研究表明，p-CA 是人酪氨酸酶的有效和选择性抑制剂，作为减色剂具有潜在的用途。
