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

作者:Liang, Lu; Gao, Chang; Luo, Meng; Wang, Wei; Zhao, Chunjian; Zu, Yuangang; Efferth, Thomas; Fu, Yujie*
来源:Journal of Agricultural and Food Chemistry, 2013, 61(11): 2755-2761.
DOI:10.1021/jf304768p

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.