title: Cajaninstilbene acid (CSA) exerts cytoprotective effects against oxidative stress through the Nrf2-dependent antioxidant pathway.
abstract: Cajaninstilbene acid (CSA), an active compound separated from pigeon pea leaves, possesses the highly efficient antioxidant activities. Transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important regulator of cellular oxidative stress. This study examined the role of Nrf2 in CSA-mediated antioxidant effects on human hepatocarcinoma (HepG2) cell line. The generation of reactive oxygen species (ROS) upon H2O2 and CSA treatment was lower than that of H2O2 alone. CSA activated Nrf2 as evaluated by Western blotting. A luciferase reporter assay also demonstrated that CSA-activated signaling resulted in the increased transcriptional activity of Nrf2 through binding to the antioxidant response element (ARE) enhancer sequence. Our study indicated that treatment of HepG2 cells with CSA induces Nrf2-dependent ARE activity and gene expression of heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and glutamate-cysteine ligase modifier subunits by activation of PI3K/AKT, ERK and JNK signaling pathways. Inhibition of Nrf2 by siRNA reduced CSA-induced upregulation of these Nrf2-related enzymes. These results suggest that the Nrf2/ARE pathway plays an important role in the regulation of CSA-mediated antioxidant effects in HepG2 cells.
authors.affiliation: State Engineering Laboratory for Bio-Resource Eco-Utilization, Northeast Forestry University, Harbin 150040, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liang
authors.forename: Meng
authors.initials: M
authors.lastname: Luo
authors.forename: Yujie
authors.initials: Y
authors.lastname: Fu
authors.forename: Yuangang
authors.initials: Y
authors.lastname: Zu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Chengbo
authors.initials: C
authors.lastname: Gu
authors.forename: Chunjian
authors.initials: C
authors.lastname: Zhao
authors.forename: Chunying
authors.initials: C
authors.lastname: Li
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
mesh_terms: D061745:Antioxidant Response Elements / Q000502:physiology; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D019610:Cytoprotection / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000502:physiology; D056945:Hep G2 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000502:physiology; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects*; D012459:Salicylates / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: C549543:3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D012459:Salicylates; D013267:Stilbenes; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human