Co-Treatment with Anthocyanins and Vitamin C Ameliorates Ethanol- Induced Neurodegeneration via Modulation of GABAB Receptor Signaling in the Adult Rat Brain

Author(s): Haroon Badshah , Tahir Ali , Ashfaq Ahmad , Min J. Kim , Noman bin Abid , Shahid A. Shah , Gwang H. Yoon , Hae Y. Lee , Myeong O. Kim .

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 14 , Issue 6 , 2015

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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.

Keywords: Anthocyanins, Apoptotic signaling pathway, γ-aminobutyric acid B1 receptor, Neuroprotection, protein kinase AcAMP response element binding protein pathway.

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Article Details

VOLUME: 14
ISSUE: 6
Year: 2015
Page: [791 - 803]
Pages: 13
DOI: 10.2174/1871527314666150225142919
Price: $58

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