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Neuroprotective, Anti-Amyloidogenic and Neurotrophic Effects of Apigenin in an Alzheimer’s Disease Mouse Model
College of Life and Environmental Sciences, Minzu University of China, 27 South Street, Zhongguancun, Beijing 100081, China
Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
* Authors to whom correspondence should be addressed.
Received: 21 June 2013; in revised form: 31 July 2013 / Accepted: 6 August 2013 / Published: 19 August 2013
Abstract: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by extracellular senile plaques and intracellular neurofibrillary tangles in the brain. Amyloid-β peptides (Aβ) are considered to play a critical role in the onset and progression of AD. Apigenin (4',5,7-trihydroxyflavone) is a pharmacologically active agent. Even though some evidence suggests that it has potential neuroprotective effects, no preexisting study has reported any therapeutic effects of apigenin in AD models. In the present study, we examined the effects of apigenin on cognitive function in APP/PS1 double transgenic AD mice and explored its mechanism(s) of action. Three-month oral treatment with apigenin rescued learning deficits and relieved memory retention in APP/PS1 mice. Apigenin also showed effects affecting APP processing and preventing Aβ burden due to the down-regulation of BACE1 and β-CTF levels, the relief of Aβ deposition, and the decrease of insoluble Aβ levels. Moreover, apigenin exhibited superoxide anion scavenging effects and improved antioxidative enzyme activity of superoxide dismutase and glutathione peroxidase. In addition, apigenin restored neurotrophic ERK/CREB/BDNF pathway in the cerebral cortex. In conclusion, apigenin may ameliorate AD-associated learning and memory impairment through relieving Aβ burden, suppressing amyloidogenic process, inhibiting oxidative stress, and restoring ERK/CREB/BDNF pathway. Therefore, apigenin appears to represent an alternative medication for the prevention and/or therapy of AD.
Keywords: Alzheimer’s disease; amyloid-β peptide; apigenin; oxidative stress; neurotrophin
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MDPI and ACS Style
Zhao, L.; Wang, J.-L.; Liu, R.; Li, X.-X.; Li, J.-F.; Zhang, L. Neuroprotective, Anti-Amyloidogenic and Neurotrophic Effects of Apigenin in an Alzheimer’s Disease Mouse Model. Molecules 2013, 18, 9949-9965.
Zhao L, Wang J-L, Liu R, Li X-X, Li J-F, Zhang L. Neuroprotective, Anti-Amyloidogenic and Neurotrophic Effects of Apigenin in an Alzheimer’s Disease Mouse Model. Molecules. 2013; 18(8):9949-9965.
Zhao, Le; Wang, Jun-Li; Liu, Rui; Li, Xiao-Xu; Li, Jian-Fei; Zhang, Lu. 2013. "Neuroprotective, Anti-Amyloidogenic and Neurotrophic Effects of Apigenin in an Alzheimer’s Disease Mouse Model." Molecules 18, no. 8: 9949-9965.