Wang Wei, Gao Ying, Wang Weiwei, Zhang Jianyong, Yin Junfeng, Le Ting, Xue Jinjin, Engelhardt Ulrich H, Jiang Heyuan
Key Laboratory of Tea Biology and Resources Utilization, Ministry of Agriculture, Tea Research Institute, Chinese Academy of Agricultural Sciences, 9 Meiling South Road, Xihu District, Hangzhou 310008, China.
Graduate School of Chinese Academy of Agricultural Sciences, 12 Zhongguancun South Street, Haidian District, Beijing 100081, China.
Antioxidants (Basel). 2022 Mar 4;11(3):502. doi: 10.3390/antiox11030502.
Kojic acid, β-arbutin, α-arbutin, and deoxyarbutin have been reported as tyrosinase inhibitors in many articles, but some contradictions exist in their differing results. In order to provide some explanations for these contradictions and to find the most suitable compound as a positive control for screening potential tyrosinase inhibitors, the activity and inhibition type of the aforementioned compounds on monophenolase and diphenolase of mushroom tyrosinase (MTYR) were studied. Their effects on B16F10 cells melanin content, tyrosinase (BTYR) activity, and cell viability were also exposed. Results indicated that α-arbutin competitively inhibited monophenolase activity, whereas they uncompetitively activated diphenolase activity of MTYR. β-arbutin noncompetitively and competitively inhibited monophenolase activity at high molarity (4000 µM) and moderate molarity (250-1000 µM) respectively, whereas it activated the diphenolase activity of MTYR. Deoxyarbutin competitively inhibited diphenolase activity, but could not inhibit monophenolase activity and only extended the lag time. Kojic acid competitively inhibited monophenolase activity and competitive-noncompetitive mixed-type inhibited diphenolase activity of MTYR. In a cellular experiment, deoxyarbutin effectively inhibited BTYR activity and reduced melanin content, but it also potently decreased cell viability. α-arbutin and β-arbutin dose-dependently inhibited BTYR activity, reduced melanin content, and increased cell viability. Kojic acid did not affect cell viability at 43.8-700 µM, but inhibited BTYR activity and reduced melanin content in a dose-dependent manner. Therefore, kojic acid was considered as the most suitable positive control among these four compounds, because it could inhibit both monophenolase and diphenolase activity of MTYR and reduce intercellular melanin content by inhibiting BTYR activity without cytotoxicity. Some explanations for the contradictions in the reported articles were provided.
在许多文章中，曲酸、β - 熊果苷、α - 熊果苷和脱氧熊果苷均被报道为酪氨酸酶抑制剂，但它们不同的结果存在一些矛盾之处。为了解释这些矛盾，并找到最合适的化合物作为筛选潜在酪氨酸酶抑制剂的阳性对照，研究了上述化合物对蘑菇酪氨酸酶（MTYR）单酚酶和二酚酶的活性及抑制类型。还考察了它们对B16F10细胞黑色素含量、酪氨酸酶（BTYR）活性和细胞活力的影响。结果表明，α - 熊果苷竞争性抑制单酚酶活性，而对MTYR的二酚酶活性呈非竞争性激活作用。β - 熊果苷在高摩尔浓度（4000 μM）时非竞争性抑制单酚酶活性，在中等摩尔浓度（250 - 1000 μM）时竞争性抑制单酚酶活性，而它能激活MTYR的二酚酶活性。脱氧熊果苷竞争性抑制二酚酶活性，但不能抑制单酚酶活性，仅延长了滞后时间。曲酸竞争性抑制单酚酶活性，对MTYR的二酚酶活性呈竞争性 - 非竞争性混合型抑制作用。在细胞实验中，脱氧熊果苷有效抑制BTYR活性并降低黑色素含量，但也显著降低细胞活力。α - 熊果苷和β - 熊果苷剂量依赖性地抑制BTYR活性、降低黑色素含量并提高细胞活力。曲酸在43.8 - 700 μM时不影响细胞活力，但剂量依赖性地抑制BTYR活性并降低黑色素含量。因此，曲酸被认为是这四种化合物中最合适的阳性对照，因为它既能抑制MTYR的单酚酶和二酚酶活性，又能通过抑制BTYR活性降低细胞内黑色素含量且无细胞毒性。文中还对报道文章中的矛盾之处提供了一些解释。
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