title: Dihydroquercetin (DHQ) induced HO-1 and NQO1 expression against oxidative stress through the Nrf2-dependent antioxidant pathway.
abstract: 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 μM, 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.
authors: Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University , Harbin 150040, PR China.
authors: Lu
authors: L
authors: Liang
authors: Chang
authors: C
authors: Gao
authors: Meng
authors: M
authors: Luo
authors: Wei
authors: W
authors: Wang
authors: Chunjian
authors: C
authors: Zhao
authors: Yuangang
authors: Y
authors: Zu
authors: Thomas
authors: T
authors: Efferth
authors: Yujie
authors: Y
authors: Fu
mesh_terms: D061745:Antioxidant Response Elements; D000975:Antioxidants / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D028221:Larix / Q000737:chemistry*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010936:Plant Extracts; D011794:Quercetin; C003377:taxifolin; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human