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Natural Dietary Supplementation of Anthocyanins via PI3K/Akt/Nrf2/HO-1 Pathways Mitigate Oxidative Stress, Neurodegeneration, and Memory Impairment in a Mouse Model of Alzheimer’s Disease

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Abstract

Well-established studies have shown an elevated level of reactive oxygen species (ROS) that induces oxidative stress in the Alzheimer’s disease (AD) patient’s brain and an animal model of AD. Herein, we investigated the underlying anti-oxidant neuroprotective mechanism of natural dietary supplementation of anthocyanins extracted from Korean black beans in the amyloid precursor protein/presenilin-1 (APP/PS1) mouse model of AD. Both in vivo (APP/PS1 mice) and in vitro (mouse hippocampal HT22 cells) results demonstrated that anthocyanins regulate the phosphorylated-phosphatidylinositol 3-kinase-Akt-glycogen synthase kinase 3 beta (p-PI3K/Akt/GSK3β) pathways and consequently attenuate amyloid beta oligomer (AβO)-induced elevations in ROS level and oxidative stress via stimulating the master endogenous anti-oxidant system of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (Nrf2/HO-1) pathways and prevent apoptosis and neurodegeneration by suppressing the apoptotic and neurodegenerative markers such as activation of caspase-3 and PARP-1 expression as well as the TUNEL and Fluoro-Jade B-positive neuronal cells in the APP/PS1 mice. In vitro ApoTox-Glo™ Triplex assay results also showed that anthocyanins act as a potent anti-oxidant neuroprotective agent and reduce AβO-induced neurotoxicity in the HT22 cells via PI3K/Akt/Nrf2 signaling. Importantly, anthocyanins improve memory-related pre- and postsynaptic protein markers and memory functions in the APP/PS1 mice. In conclusion, our data suggested that consumption and supplementation of natural-derived anti-oxidant neuroprotective agent such as anthocyanins may be beneficial and suggest new dietary-supplement strategies for intervention in and prevention of progressive neurodegenerative diseases, such as AD.

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Acknowledgements

This research was supported by the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (2016M3C7A1904391).

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Authors and Affiliations

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

    Tahir Ali, Taehyun Kim, Shafiq Ur Rehman, Muhammad Sohail Khan, Faiz Ul Amin, Mehtab Khan, Muhammad Ikram & Myeong Ok Kim

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  1. Tahir Ali
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  7. Muhammad Ikram
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  8. Myeong Ok Kim
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Correspondence to Myeong Ok Kim.

Ethics declarations

The animal maintenance, treatments, behavioral studies and surgical procedures were carried out in accordance with the animal ethics committee (IACUC) guidelines issued by the Division of Applied Life Sciences, Department of Biology at Gyeongsang National University, South Korea. The experimental methods with animals were carried out in accordance with the approved guidelines (Approval ID: 125) and all experimental protocol were approved by the animal ethics committee (IACUC) of the Division of Applied Life Sciences, Department of Biology at Gyeongsang National University, South Korea.

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The authors declared no conflict of interest.

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Ali, T., Kim, T., Rehman, S.U. et al. Natural Dietary Supplementation of Anthocyanins via PI3K/Akt/Nrf2/HO-1 Pathways Mitigate Oxidative Stress, Neurodegeneration, and Memory Impairment in a Mouse Model of Alzheimer’s Disease. Mol Neurobiol 55, 6076–6093 (2018). https://doi.org/10.1007/s12035-017-0798-6

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  • DOI: https://doi.org/10.1007/s12035-017-0798-6

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