title: Activation of the phase II enzymes for neuroprotection by ginger active constituent 6-dehydrogingerdione in PC12 cells.
abstract: The cellular endogenous antioxidant system plays pivotal roles in counteracting or retarding the pathogenesis of many neurodegenerative diseases. Molecules with the ability to enhance the antioxidant defense thus are promising candidates for neuroprotective drugs. 6-Dehydrogingerdione (6-DG), one of the major components of dietary ginger, has received increasing attention due to its multiple pharmacological activities. However, how this pleiotropic molecule works on the neuronal system has not been studied. This paper reports that 6-DG efficiently scavenges various free radicals in vitro and displays remarkable cytoprotection against oxidative stress-induced neuronal cell damage in the neuron-like rat pheochromocytoma cell line, PC12 cells. Pretreatment of PC12 cells with 6-DG significantly up-regulates a panel of phase II genes as well as the corresponding gene products, such as glutathione, heme oxygenase,
  quinone oxidoreductase, and thioredoxin reductase. Mechanistic study indicates that activation of the Keap1-Nrf2-ARE pathway is the molecular basis for the cytoprotection of 6-DG. This is the first revelation of this novel mechanism of 6-DG as an Nrf2 activator against oxidative injury, providing the potential therapeutic use of 6-DG as neuroprotective agent.
authors.affiliation: State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University , Lanzhou, Gansu 730000, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Yao
authors.forename: Chunpo
authors.initials: C
authors.lastname: Ge
authors.forename: Dongzhu
authors.initials: D
authors.lastname: Duan
authors.forename: Baoxin
authors.initials: B
authors.lastname: Zhang
authors.forename: Xuemei
authors.initials: X
authors.lastname: Cui
authors.forename: Shoujiao
authors.initials: S
authors.lastname: Peng
authors.forename: Yaping
authors.initials: Y
authors.lastname: Liu
authors.forename: Jianguo
authors.initials: J
authors.lastname: Fang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005233:Fatty Alcohols / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D020939:Zingiber officinale / Q000737:chemistry*; D005978:Glutathione / Q000378:metabolism; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C555348:6-dehydrogingerdione; D000975:Antioxidants; D005233:Fatty Alcohols; D016166:Free Radical Scavengers; D047908:Intracellular Signaling Peptides and Proteins; C486610:KEAP1 protein, rat; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495637:Nfe2l2 protein, rat; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D006139:Guaiacol; D006419:Heme Oxygenase (Decyclizing); D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D013880:Thioredoxin-Disulfide Reductase; C505410:Casp3 protein, rat; D053148:Caspase 3; D005978:Glutathione