Effect of Quercetin on PC12 Alzheimer’s Disease Cell Model Induced by Aβ_25-35 and Its Mechanism Based on Sirtuin1/Nrf2/HO-1 Pathway

Abstract

Objective. This study is aimed at studying the effect of quercetin on the Alzheimer disease cell model induced by Aβ25-35 in PC12 cells and its mechanism of action. Methods. The AD cell model was established by Aβ25-35. Quercetin was used at different concentrations (0, 10, 20, 40, and 80 μmol/L). The morphology of cells was observed, and the effect on cell survival rate was detected by the MTT method. Cell proliferation was detected by the SRB method. The contents of LDH, SOD, MDA, GSH-Px, AChE, CAT, and T-AOC were detected by kits. The expression of sirtuin1/Nrf2/HO-1 was detected by RT-qPCR and Western blot. Results. PC12 cells in the control group grew quickly and adhered well to the wall, most of which had extended long axons and easily grew into clusters. In the model group, cells were significantly damaged and the number of cells was significantly reduced. It was found that PC12 cells were swollen, rounded, protruding, and retracting, with reduced adherent function and floating phenomenon. Quercetin could increase the survival rate and proliferation rate of PC12 cells; reduce the levels of LDH, AChE, MDA, and HO-1 protein; and increase the levels of SOD, GSH-Px, CAT, T-AOC, sirtuin1, and Nrf2 protein. Conclusion. Quercetin can increase the survival rate of PC12 injured by Aβ25-35, promote cell proliferation, and antagonize the toxicity of Aβ; it also has certain neuroprotective effects. Therefore, quercetin is expected to become a drug for the treatment of AD.

Association Between Dietary Flavonoids Intake and Cognitive Function in an Italian Cohort

“…Among the compounds found to be associated with better cognitive health in our study, flavonols and flavanones have been shown to increase the transforming growth factor-β1 (TGF-β1) levels [ 42 , 43 ], a neurotrophic factor that exerts a key role in recognition memory formation, and a deficit of TGF-b1 signaling can contribute to cognitive decline in Alzheimer’s disease [ 44 , 45 ]. With special regard to quercetin (a flavonol found related to better cognitive health in our study), it has demonstrated effectiveness in animal models of Alzheimer’s disease in decreasing of oxidative stress [ 46 ] and positively modulating Nrf2/HO-1 (nuclear factor erythroid 2–related factor 2/heme oxygenase-1) pathway [ 47 ]; also, an effect toward neuro-inflammation through regulation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and has been observed [ 48 ]. Furthermore, quercetin has been shown to induce the expression of a brain-derived neurotrophic factor (BDNF) [ 49 ] as well as a nerve growth factor (NGF) [ 50 ], which are the most studied and best-characterized neurotrophins of the central nervous system, involved in the modulation of synaptic plasticity and adult neurogenesis.…”

Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery

“…As it was discussed earlier, plant derived-natural compounds are able to regulate Nrf2 signaling in exerting their protective effect against oxidative stress-mediated diseases [86][87][88]. Pristimerin (Pris) is a natural triterpenoid compound derived from Celastraceae plant with different pharmacological activities such as anti-tumor, anti-inflammatory and antioxidant [89,90].…”

Fucoxanthin Prevents 6‐OHDA‐Induced Neurotoxicity by Targeting Keap1

“…RT-qPCR was performed on a LightCycler 96 Real-Time PCR System (Roche, Switzerland) using SYER-Green I. Nine pairs of specific primers were designed as follows [22][23][24]: for zebrafish: Keap1 forward 5 ′ -TGTGAT CTGGTTCTGCATGTC-3 ′ and reverse 5 ′ -ACTCCTTGA AGTTGCTGGTG-3 ′ ; Nrf2 forward 5 ′ -CTGCTGTCACT CCCAGAGTT-3 ′ and reverse 5 ′ -GCCGTAGTTTTGGG TTGGTG-3 ′ ; HO-1 forward 5 ′ -AAGAGCTGGACAGAAA CGCA-3 ′ and reverse 5 ′ -AGAAGTGCTCCAAGTCCTGC-3′; GCLC forward 5′-CTCCTCACAGTCACGGCATT-3′ and reverse 5′-TGAATGGAGACGGGGTGTTG-3′; GCLM forward 5′-AAGCCAGACACTGACACACC-3′ and reverse 5 ′ -ATCTGGAGGCATCACACAGC-3 ′ ; β-actin forward 5 ′ -CACTGAGGCTCCCCTGAATC-3′ and reverse 5′-GGGT CACACCATCACCAGAG-3 ′ ; for PC12 cells: Nrf2 forward 5 ′ -TGGTGGTTTGCTACGACG-3 ′ and reverse 5 ′ -CTCC AGAACTCC AGGCGG-3 ′ ; β-actin forward 5 ′ -ATGGCA ACTGTCCCTGAACT-3 ′ and reverse 5 ′ -GTCATC ATCC CACGAGTCAC-3 ′ . All primers were synthesized by Invitrogen (Shanghai, China), and β-actin was adopted as a housekeeping gene.…”