title: Co-Treatment with Anthocyanins and Vitamin C Ameliorates Ethanol- Induced Neurodegeneration via Modulation of GABAB Receptor Signaling in the Adult Rat Brain.
abstract: Chronic ethanol exposure is known to cause neuronal damage in both humans and experimental animal models. Ethanol treatment induces neurotoxicity via the generation of reactive oxygen species (ROS), while anthocyanins (extracted from black soybean) and ascorbic acid (vitamin C) are free radical scavengers that can be used as neuroprotective agents against ROS. In this study the underlying neuroprotective potential of black soybean anthocyanins and vitamin C was determined. For this purpose, adult rats were exposed to 10% (v/v) ethanol for 8 weeks, followed by co-treatment with anthocyanins (24 mg/kg) and vitamin C (100 mg/kg) during the last 4 weeks. Our results showed that ethanol administration increased the expression of γ -aminobutyric acid B1 receptor (GABAB1R) and induced neuronal apoptosis via alterations to the Bax/Bcl-2 ratio, release of cytochrome C and activation of caspase-3 and caspase-9. Anthocyanins alone and supplementation with vitamin C showed an additive effect in reversing the trend of apoptotic signals induced by ethanol in the cortex and hippocampus. Consequently, anthocyanins also decreased the expression of poly (ADP ribose) polymerase-1 induced by ethanol and prevented DNA damage. Furthermore, anthocyanins and vitamin C reversed the ethanol-induced expression of GABAB1R and its downstream signaling molecule phospho-cAMP response element binding protein. Moreover, histopathology and immunohistochemistry results showed that anthocyanins and vitamin C significantly reduced ethanol-induced neuronal cell death. Our study revealed a neuroprotective role of anthocyanins and vitamin C via modulation of GABAB1R expression in the adult brain. Hence, we suggest that anthocyanins or co-treatment with anthocyanins and vitamin C may be a new and potentially effective neuroprotective agent for alcohol abuse.
authors.forename: Haroon
authors.initials: H
authors.lastname: Badshah
authors.forename: Tahir
authors.initials: T
authors.lastname: Ali
authors.forename: Ashfaq
authors.initials: A
authors.lastname: Ahmad
authors.forename: Min J
authors.initials: MJ
authors.lastname: Kim
authors.forename: Noman Bin
authors.initials: NB
authors.lastname: Abid
authors.forename: Shahid A
authors.initials: SA
authors.lastname: Shah
authors.forename: Gwang H
authors.initials: GH
authors.lastname: Yoon
authors.forename: Hae Y
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Department of Biology, College of Natural Sciences, Gyeongsang National University, Jinju 660- 701, South Korea. mokim@gsnu.ac.kr.
authors.forename: Myeong O
authors.initials: MO
authors.lastname: Kim
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002492:Central Nervous System Depressants; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D000431:Ethanol / Q000633:toxicity; D008297:Male; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000872:Anthocyanins; D000975:Antioxidants; D002492:Central Nervous System Depressants; D018080:Receptors, GABA-B; D000431:Ethanol; D050882:CREB-Binding Protein; D053148:Caspase 3; D001205:Ascorbic Acid