Characterization of tangeretin as an activator of nuclear factor erythroid 2-related factor 2/antioxidant response element pathway in HEK293T cells
文献类型： 外文期刊
作者： Lv, Chengyu 1 ; Li, Yuqiu 2 ; Liang, Rong 3 ; Huang, Wei 2 ; Xiao, Yechen 1 ; Ma, Xinqi 2 ; Wang, Yongjun 2 ; Zou, Haoyang 1 ; Qin, Fen 2 ; Sun, Chang 2 ; Li, Tiezhu 2 ; Zhang, Jie 1 ;
作者机构： 1.Jilin Univ, Coll Food Sci & Engn, Changchun 130062, Peoples R China
2.Jilin Acad Agr Sci, Inst Agrofood Technol, Changchun 130033, Peoples R China
3.Liaocheng Univ, Agr Sci & Engn Sch, Liaocheng 252059, Peoples R China
关键词： Tangeretin; Nuclear factor erythroid 2 -related factor 2; Antioxidant response element; Molecular docking
期刊名称：CURRENT RESEARCH IN FOOD SCIENCE （ 影响因子：6.3； 五年影响因子：6.3 ）
ISSN：
年卷期： 2023 年 6 卷
页码：
收录情况： SCI
摘要： Numerous studies have reported that tangeretin is a polymethoxylated flavone with a variety of biological activates, but little research has been done on the antioxidant mechanism of tangeretin. Hence, we investigated the effect of tangeretin on the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway and its potential molecular mechanisms by in vitro and in silico research. The results of molecular docking suggested that tangeretin bound at the top of the central pore of Kelch-like ECH-associated protein 1 (Keap1) Kelch domain, and the hydrophobic and hydrogen bond interactions contributed to their stable binding. Herein, the regulation of Nrf2-ARE pathway by tangeretin was explored in the human embryonic kidney cell line HEK293T, which is relatively easy to be transfected. Upon binding to tangeretin, Nrf2 translocated to the nucleus of HEK293T cells, which in turn activated the Nrf2-ARE pathway. Luciferase reporter gene analysis showed that tangeretin significantly induced ARE-mediated transcriptional activation. Real-time PCR and Western blot assays showed that tangeretin induced the gene and protein expressions of Nrf2-mediated targets, including heme oxygenase 1 (HO-1), nicotinamide adenine dinucleotide phosphate (NADPH) quinone dehydrogenase 1 (NQO1), and glutamate-cysteine ligase (GCLM). In addition, tangeretin could effectively scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals. In summary, tangeretin may be a potential antioxidant via activating the Nrf2ARE pathway.
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