title: Hesperidin attenuates learning and memory deficits in APP/PS1 mice through activation of Akt/Nrf2 signaling and inhibition of RAGE/NF-κB signaling.
abstract: 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.
authors.affiliation: The Fifth Department of Tianjin Huanhu Hospital, No. 122, Qixiangtai Road, Hexi District, Tianjin, 300060, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hong
authors.affiliation: The Fifth Department of Tianjin Huanhu Hospital, No. 122, Qixiangtai Road, Hexi District, Tianjin, 300060, People's Republic of China. hysubmit@163.com.
authors.forename: Zhongping
authors.initials: Z
authors.lastname: An
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D002678:Chimera; D004195:Disease Models, Animal; D006569:Hesperidin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy; D051379:Mice; D008822:Mice, Transgenic; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D053764:Presenilin-1 / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: C000593873:Ager protein, mouse; D016564:Amyloid beta-Protein Precursor; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D018696:Neuroprotective Agents; C495636:Nfe2l2 protein, mouse; C508853:PSEN1 protein, human; D053764:Presenilin-1; D000067759:Receptor for Advanced Glycation End Products; D006569:Hesperidin; D051057:Proto-Oncogene Proteins c-akt
keywords: Alzheimer disease; Hesperidin; NF-κB; Nrf2; RAGE