title: Cyanidin-3-glucoside ameliorates ethanol neurotoxicity in the developing brain.
abstract: Ethanol exposure induces neurodegeneration in the developing central nervous system (CNS). Fetal alcohol spectrum disorders (FASD) are caused by ethanol exposure during pregnancy and are the most common nonhereditary cause of mental retardation. It is important to identify agents that provide neuroprotection against ethanol neurotoxicity. Multiple mechanisms have been proposed for ethanol-induced neurodegeneration, and oxidative stress is one of the most important mechanisms. Recent evidence indicates that glycogen synthase kinase 3β (GSK3β) is a potential mediator of ethanol-mediated neuronal death. Cyanidin-3-glucoside (C3G), a member of the anthocyanin family, is a potent natural antioxidant. Our previous study suggested that C3G inhibited GSK3β activity in neurons. Using a third trimester equivalent mouse model of ethanol exposure, we tested the hypothesis that C3G can ameliorate ethanol-induced neuronal death in the developing brain. Intraperitoneal injection of C3G reduced ethanol-meditated caspase-3 activation, neurodegeneration, and microglial activation in the cerebral cortex of 7-day-old mice. C3G blocked ethanol-mediated GSK3β activation by inducing phosphorylation at serine 9 while reducing the phosphorylation at tyrosine 216. C3G also inhibited ethanol-stimulated expression of malondialdehyde (MDA) and p47phox, indicating that C3G alleviated ethanol-induced oxidative stress. These results provide important insight into the therapeutic potential of C3G.
authors.affiliation: Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA.
authors.forename: Zunji
authors.initials: Z
authors.lastname: Ke
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Fan
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Mei
authors.initials: M
authors.lastname: Xu
authors.forename: Kimberley A
authors.initials: KA
authors.lastname: Bower
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Frank
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Ou
authors.forename: Xianglin
authors.initials: X
authors.lastname: Shi
authors.forename: Jia
authors.initials: J
authors.lastname: Luo
mesh_terms: D020268:Alcohol-Induced Disorders, Nervous System / Q000188:drug therapy*; D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000196:embryology*; D004195:Disease Models, Animal; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000188:drug therapy*; D005960:Glucosides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011247:Pregnancy
chemical_list: D000872:Anthocyanins; D005960:Glucosides; D018696:Neuroprotective Agents; C462279:cyanidin-3-O-beta-glucopyranoside; D000431:Ethanol