School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China.
College of Chemistry, Green Catalysis center, Henan Joint International Research Laboratory of Green Construction of Functional Molecules and Their Bioanalytical Applications, Zhengzhou University, Zhengzhou 450001, PR China.
Int J Biol Macromol. 2020 Oct 1;160:153-163. doi: 10.1016/j.ijbiomac.2020.05.193. Epub 2020 May 25.
In this study, the inhibitory effects of four anthraquinones including chrysophanol, emodin, physcione and rhein on tyrosinase were investigated by enzyme inhibition assay. The results indicated that all of anthraquinones could significantly inhibit the activity of tyrosinase in a competitive manner. To gain insight into the inhibitory mechanism of anthraquinones on tyrosinase, spectroscopic analysis combined with molecular docking studies were performed. Fluorescence results showed that anthraquinones interacted with tyrosinase by static quenching in a molecular ratio of 1:1. Circular dichroism and molecular docking suggested that anthraquinones could not chelate directly the copper ions but they could bind to amino acid residues in the active site of tyrosinase via electrostatic forces and hydrophobic interactions, as well as hydrogen bonds, and the binding processes resulted in the conformational changes of tyrosinase and prevented the substrate (L-DOPA) from entering the active site, which led to the decrease of tyrosinase activity. Our study in this paper provides a scientific basis for revealing the inhibition of tyrosinase activity by anthraquinone compounds. As a natural inhibitor of tyrosinase, anthraquinones can be used as a potential agent to reduce enzymatic browning reactions, such as food browning and melanization of skin.
在这项研究中，通过酶抑制试验研究了四种蒽醌类化合物（大黄酚、大黄素、大黄酸和rhein）对酪氨酸酶的抑制作用。结果表明，所有蒽醌类化合物均能以竞争性方式显著抑制酪氨酸酶的活性。为了深入了解蒽醌类化合物对酪氨酸酶的抑制机制，进行了光谱分析结合分子对接研究。荧光结果表明，蒽醌类化合物通过静态猝灭以 1:1 的分子比与酪氨酸酶相互作用。圆二色性和分子对接表明，蒽醌类化合物不能直接螯合铜离子，但可以通过静电力和疏水相互作用以及氢键与酪氨酸酶的活性位点结合，结合过程导致酪氨酸酶构象发生变化，阻止底物（L-DOPA）进入活性位点，从而降低酪氨酸酶的活性。本文的研究为揭示蒽醌类化合物对酪氨酸酶活性的抑制作用提供了科学依据。作为酪氨酸酶的天然抑制剂，蒽醌类化合物可用作减少酶促褐变反应的潜在剂，如食品褐变和皮肤黑化。
