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KMID : 0043320180410060655
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Archives of Pharmacal Research
2018 Volume.41 No. 6 p.655 ~ p.663
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Hesperidin attenuates learning and memory deficits in APP/PS1 mice through activation of Akt/Nrf2 signaling and inhibition of RAGE/NF-κB signaling
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Hong Yan
An Zhongping
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Abstract
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Numerous studies have demonstrated that oxidative stress and inflammation play a pivotal role in the pathophysiology of Alzheimer disease (AD). Hesperidin (HP) has various pharmacological effects including anti-oxidative, anti-inflammatory and neuroprotective properties. In this study, APP/PS1 mice were used to evaluate the neuroprotective effects of HP. We reported that intragastric administration of HP (40 mg/kg) for 90 days significantly attenuated cognitive impairment in APP/PS1 mice. HP treatment suppressed oxidative stress by reducing the levels of ROS, LPO, protein carbonyl and 8-OHdG and increasing the activity of HO-1, SOD, catalase, and GSH-Px. HP treatment also inhibited inflammation by decreasing the levels of TNF-α, C-reactive protein and MCP-1 and reducing the activity of NF-κB. Moreover, HP could reverse the decreased phosphorylation of Akt, the decreased phosphorylation of GSK-3β, the lessened Nrf2 and the reduced expression of HO-1. HP could also inhibit the increased the RAGE expression, the enhanced phosphorylation of IκBα, and the augmented nuclear translocation of NF-κB/p65 in cortex of APP/PS1 mice. Taken together, HP suppresses oxidative stress and inflammation via activation of Akt/Nrf2 signaling and inhibition of RAGE/NF-κB signaling and further confers neuroprotection.
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KEYWORD
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Alzheimer disease, Hesperidin, Nrf2, RAGE, NF-κB
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