Dihydroquercetin (DHQ) Induced HO-1 and NQO1 Expression against Oxidative Stress through the Nrf2-Dependent Antioxidant Pathway

被引:97
作者
Liang, Lu [1 ,2 ]
Gao, Chang [3 ]
Luo, Meng [1 ,2 ]
Wang, Wei [1 ,2 ]
Zhao, Chunjian [1 ,2 ]
Zu, Yuangang [1 ]
Efferth, Thomas [4 ]
Fu, Yujie [1 ,2 ]
机构
[1] Northeast Forestry Univ, Minist Educ, Engn Res Ctr Forest Biopreparat, Harbin 150040, Peoples R China
[2] Northeast Forestry Univ, Minist Educ, Key Lab Forest Plant Ecol, Harbin 150040, Peoples R China
[3] Peking Univ, Hlth Sci Ctr, Coll Basic Med Sci, Beijing 100083, Peoples R China
[4] Johannes Gutenberg Univ Mainz, Inst Pharm & Biochem, Dept Pharmaceut Biol, D-55128 Mainz, Germany
关键词
dihydroquercetin; antioxidant activity; Nrf2; antioxidant genes; RADICAL SCAVENGING ACTIVITY; SUBUNIT GENE; ACTIVATION; FLAVONOIDS; GLUTATHIONE; RESISTANCE; QUERCETIN; INDUCTION; TAXIFOLIN; OXIDASE;
D O I
10.1021/jf304768p
中图分类号
S [农业科学];
学科分类号
09 ;
摘要
Dihydroquercetin (DHQ) is a well-known antioxidant agent. In the present investigation, we reported for the first time that DHQ stimulates the expression of phase II detoxifying enzymes through the Nrf2-dependent signaling pathway. The IC50 values of DHQ for reduction of 2,2-diphenyl-1-picrylhydrazol (DPPH), reducing power assay, lipid peroxidation assay, and xanthine oxidase inhibition were 5.96, 4.31, 2.03, and 13.24 mu M, respectively. DHQ possessed considerable protective activity from oxidative DNA damage. A luciferase reporter assay also demonstrated that DHQ-activated signaling resulted in the increased transcriptional activity of Nrf2 through binding to the ARE (antioxidant response element) enhancer sequence. Furthermore, Western blotting and luciferase assay revealed DHQ activated ERK1/2, Akt, and JNK signaling pathways, subsequently leading to Nrf2 nuclear translocation. DHQ upregulated the Nrf2-related antioxidant genes heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO1), and glutamate-cysteine ligase modifier subunits. Inhibition of Nrf2 by siRNA reduced DHQ:induced upregulation of these antioxidant genes.
引用
收藏
页码:2755 / 2761
页数:7
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