Naringenin improves learning and memory in an Alzheimer's disease rat model: Insights into the underlying mechanisms

Abstract

Alzheimer's disease (AD) is one of the prevalent neurological disorders of the central nervous system hallmarked by increased beta-amyloid (Aβ) deposition and ensuing learning and memory deficit. In the present study, the beneficial effect of naringenin on improvement of learning and memory was evaluated in an Alzheimer's disease rat model. The Aβ-injected rats showed a lower alternation score in Y-maze task, impairment of retention and recall capability in passive avoidance test, and lower correct choices and higher errors in radial arm maze (RAM) task as compared to sham group in addition to enhanced oxidative stress and apoptosis. Naringenin, but not a combination of naringenin and fulverstrant (an estrogenic receptor antagonist) significantly improved the performance of Aβ-injected rats in passive avoidance and RAM tasks. Naringenin pretreatment of Aβ-injected rats also lowered hippocampal malondialdehyde (MDA) with no significant effect on nitrite and superoxide dismutase (SOD) activity in addition to lowering apoptosis. These results suggest naringenin pretreatment attenuates Aβ-induced impairment of learning and memory through mitigation of lipid peroxidation and apoptosis and its beneficial effect is somewhat mediated via estrogenic pathway.

A Systematic Strategy for Discovering a Therapeutic Drug for Alzheimer’s Disease and Its Target Molecule

“…Twenty-three milligram naringenin is contained in 500 mg DR extract. We also referred to the dose of naringenin in reports of other AD models (Yang et al, 2014; Ghofrani et al, 2015). We orally administered naringenin (5 and 100 mg kg -1 per day) to the 5XFAD mice (male, 8–12 months old) for 31 days ( Figure 5A ).…”

“…Naringenin has been reported to improve learning and memory in Aβ or streptozotocin-injected AD models (Yang et al, 2014; Ghofrani et al, 2015), which might relate to the mitigation of lipid peroxidation and apoptosis or the increased insulin and insulin receptor expression in the rat brain. Naringenin also showed anti-inflammatory activity in LPS/IFN-γ-stimulated glial cells and neuroprotective effects against H 2 O 2 -induced hyper-oxidation (Heo et al, 2004; Vafeiadou et al, 2009).…”

Effects of porcine brain hydrolysate on impairment of cognitive learning ability in amyloid β(1–40)‐infused rats

“…As shown in Figure , we measured the MDA levels of cerebal cortex and hippocampus in Aβ infused rat administrated the PBH. The MDA was known and often used as a marker of oxidation index (Ghofrani et al., ). The results were administering PBH in the EP‐M and EP‐H groups significantly reduced cerebral cortical and hippocampal MDA levels, compared with the control group ( p < .05).…”

Nonpharmacological treatment options for Alzheimer’s disease: from animal testing to clinical studies

“…Reducing Aβ1-42 accumulation and levels of APP, inhibiting BACE1 activity (Liu et al, 2017) Curcumin Activating neuronal nitric oxide pathway Caffeic acid Blocking Aβ formation and aggregation (Habtemariam, 2016) Epigallocatechin Modulating the enzymes involved in APP processing and reducing the formation of Aβ (Rezai-Zadeh, 2005) Ferulic acid Exerting antiinflammatory actions (Ghosh et al, 2017) Gallic acid Preventing fibril formation by Aβ peptide (Liu et al, 2013) Genistein Modulating neuroinflammation, Aβ deposition, and tau hyperphosphorylation (Park et al, 2016) Hesperidin Exhibiting high-affinity BACE1 inhibitor, preventing Aβ fibril formation (Chakraborty et al, 2016) Honokiol Modulating excitotoxicity associated with the blockade of glutamate receptors and reducing neuroinflammation (Talarek et al, 2017) Icariin Preventing Aβ1-42 aggregation (Liu et al, 2015) Leucomicin Preventing Aβ1-42 induced oxidative stress (Türkez, 2018) Lycopene Inhibiting NF-κB activity and regulating neuroinflammatory cytokines (Sachdeva and Chopra, 2015) Naringenin Alleviating Aβ-induced impairments, lipid peroxidation, and apoptosis via the estrogenic pathway. (Ghofrani et al, 2015) Nobiletin Reducing Aβ plaques, NFTs, and cognitive impairments (Nakajima et al, 2015) Oleuropein Counteracting amyloid-β peptide and tau aggregation (Martorell et al, 2016) Quercetin Minimizing Aβ1-40 and Aβ1-42 amounts, decreasing BACE1-mediated cleavage of APP (Sabogal-Guáqueta et al, 2015) Rosmarinic acid Preventing Aβ-sheet assembly (Cornejo et al, 2017) Resveratrol Promoting the removal of Aβ peptides and antiinflammatory content (Braidy et al, 2016) Rutin Inhibiting Aβ aggregation, supporting antioxidant SOD, CAT, and GSH-Px enzyme activities (Yu et al, 2015) Sulforaphane Reducing cholinergic neuron loss (Zhang et al, 2014) Tangeretin Alleviating cholinergic deficits, reducing Aβ accumulation, inhibiting tau hyperphosphorylation and increasing NEP levels (Braidy et al, 2017a) Tannic acid…”