Sun Shibo, Zhang Yici, Xu Weiping, Zhang Yue, Yang Rui, Guo Jianli, Guan Shui, Ma Qiang, Ma Kun, Xu Jianqiang
School of Life and Pharmaceutical Sciences (LPS), Panjin Institute of Industrial Technology (PIIT), Liaoning Key Laboratory of Chemical Additive Synthesis and Separation (CASS), Dalian University of Technology, Panjin 124221, China.
Interdisciplinary Research Center on Biology and Chemistry (IRCBC), Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China.
Antioxidants (Basel). 2021 Oct 29;10(11):1733. doi: 10.3390/antiox10111733.
Food colorants are widely used by humans in food production and preparation; however, their potential toxicity requires an in-depth analysis. In this study, five out of 15 commercial food colorants, namely, lutein, betanin, caramel, crocin and chlorophyll, significantly inhibited wild type selenoprotein thioredoxin reductase 1 (TrxR1, TXNRD1) in vitro. The hyperactive Sec residue of TrxR1 was targeted by those five colorants, which was confirmed by the site-directed mutagenesis of TrxR1. Furthermore, two colorants, chlorophyll and betanin, triggered the oligomerization of TrxR1. A chlorophyll-derived compound, chlorophyllin, irreversibly inhibited the 5,5'-dithiobis-2-nitrobenzoic acid (DTNB) reducing activity of TrxR1 with = 6.96 × 10 ± 0.49 × 10 µM min. Moreover, chlorophyllin reduced the cellular TrxR activity, leading to reactive oxygen species (ROS) accumulation and, subsequently, promoting cancer cell death. In conclusion, this study might contribute to understand the food safety of commercial colorants and provide chemotherapeutic compounds by targeting TrxR1.
食用色素在食品生产和制备过程中被人类广泛使用；然而，其潜在毒性需要深入分析。在本研究中，15种商用食用色素中的5种，即叶黄素、甜菜红素、焦糖、藏红花素和叶绿素，在体外显著抑制野生型硒蛋白硫氧还蛋白还原酶1（TrxR1，TXNRD1）。TrxR1的高活性硒代半胱氨酸残基是这5种色素的作用靶点，这通过TrxR1的定点诱变得到证实。此外，两种色素，叶绿素和甜菜红素，引发了TrxR1的寡聚化。一种叶绿素衍生化合物，叶绿酸，以 = 6.96 × 10 ± 0.49 × 10 µM min不可逆地抑制TrxR1的5,5'-二硫代双-2-硝基苯甲酸（DTNB）还原活性。此外，叶绿酸降低细胞TrxR活性，导致活性氧（ROS）积累，随后促进癌细胞死亡。总之，本研究可能有助于理解商用色素的食品安全问题，并通过靶向TrxR1提供化疗化合物。
