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Anthocyanins Reversed D-Galactose-Induced Oxidative Stress and Neuroinflammation Mediated Cognitive Impairment in Adult Rats

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Abstract

Aging is a major factor involved in neurological impairments, decreased anti-oxidant activities, and enhanced neuroinflammation. D-galactose (D-gal) has been considered an artificial aging model which induces oxidative stress and inflammatory response resulting in memory and synaptic dysfunction. Dietary supplementation exerts valuable effects against oxidative stress and neuroinflammation. Polyphenolic flavonoids, such as anthocyanins, have been reported as an anti-inflammatory and anti-oxidant agents against various neurodegenerative diseases. Recently, our group reported anthocyanin neuroprotection of the developing rat brain against ethanol-induced oxidative stress and neurodegenaration and ethanol-induced neuronal apoptosis via GABAB1 receptor intracellular signaling in prenatal rat hippocampus. Here, we examined the protective effect of anthocyanin neuroprotection against D-gal-induced oxidative and inflammatory response in the hippocampus and cortex regions and explore the potential mechanism of its action. Our results indicated that anthocyanins treatment significantly improved behavioral performance of D-gal-treated rats in Morris water maze and Y-maze tests. One of the potential mechanisms of this action was decreased expression of the receptor for advance glycation end product, reduced level of reactive oxygen species (ROS) and lipid peroxidation as well as markers of the Alzheimer’s disease. Furthermore, the results also indicated that anthocyanins inhibited activated astrocytes and neuroinflammation via suppression of various inflammatory markers including p-NF- K B, inducible nitric oxide synthase (iNOS), and tumor necrosis factor-alpha (TNF-α) in the hippocampus and cortex regions of D-gal-treated rats brain. Moreover, anthocyanins abrogated neuroapoptosis via C-jun N-terminal kinase (p-JNK) suppression and improved deregulated synaptic proteins including synaptophysin, synaptosomal-associated protein (SNAP)-23, SNAP-25, and phosphorylated CREB. This data suggests that anthocyanins could be a safe and promising anti-oxidant and anti-neuroinflammatory agent for age-related neurodegenerative diseases such as Alzheimer’s disease.

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Abbreviations

PBS:

Phosphate buffer saline

BACE-1:

Beta-site APP cleaving enzyme-1

NF-KB:

Nuclear factor kappa B

TNF-α:

Tumer necrosis factor-alpha

iNOS:

Inducible nitric oxide synthase

p-JNK:

C-jun N-terminal kinase

PARP-1:

Poly[ADP-ribose] polymerase 1

TRITC:

Tetramethyl rhodamine isothiocyanate

FITC:

Fluorescein isothiocyanate

DG:

Dentate gyrus

SNAP-23:

Synaptosomal-associated protein 23

S.D:

Standard deviation

i.p.:

Intraperitoneally

ROS:

Reactive oxygen species

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Acknowledgments

This research was supported by the Pioneer Research Center Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT and Future Planning (2012–0009521)

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Authors and Affiliations

  1. Department of Biology and Applied Life Science (BK 21), College of Natural Sciences (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea

    Shafiq Ur Rehman, Shahid Ali Shah, Tahir Ali & Myeong Ok Kim

  2. Department of Agronomy, Research Institute of Life Science, Gyeongsang National University, Jinju, 660-701, South Korea

    Jong Il Chung

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  1. Shafiq Ur Rehman
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Correspondence to Myeong Ok Kim.

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Mr. Shafiq Ur Rehman and Mr. Shahid Ali Shah contributed equally to this work.

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Rehman, S.U., Shah, S.A., Ali, T. et al. Anthocyanins Reversed D-Galactose-Induced Oxidative Stress and Neuroinflammation Mediated Cognitive Impairment in Adult Rats. Mol Neurobiol 54, 255–271 (2017). https://doi.org/10.1007/s12035-015-9604-5

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