Quercetin exhibits neuroprotective effect by reduc-ing amyloid precursor protein expression and oxida-tive stress in Neuro2a/APPswe cell model
10.3867/j.issn.1000-3002.2023.07.096
- Author:
Zhi TANG
1
,
2
;
Min GUO
;
Yaqian PENG
;
Ting ZHANG
;
Yan XIAO
;
Ruiqing NI
;
Xiaolan QI
Author Information
1. Key Laboratory of Endemic and Ethnic Diseases,Ministry of Education and Key Laboratory of Medical Molecular Biol-ogy of Guizhou Province,Guizhou Medical University,Gui-yang 550000,China
2. Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry,Gui-yang 550000,China
- Keywords:
quercetin;
mitochondrial dysfunction;
oxida-tive stress;
ERK1/2 pathway;
Akt pathway
- From:
Chinese Journal of Pharmacology and Toxicology
2023;37(7):520-520
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE The abnormal amyloid-β(Aβ)and oxidative stress assiociated with the progression of Alzheimer disease(AD).Quercetin has been reported to possess antioxidant and anti-inflammatory properties in neurodegenerative disorders.In this present study,we designed to characterize the mechanisms by which quer-cetin exerts neuroprotective effects in murine neuroblas-toma N2a cells stably expressing human Swedish mutant amyloid precursor protein(N2a/APP).METHODS N2a/APP cells were treated with quercetin at concentrations of 10,20 and 50 μ mol·L-1 for 24 h.Cell viability was examined with CCK-8 assays.The protein levels of ERK1/2 and Akt were detected by Western blotting.Intra-cellular reactive oxygen species(ROS)was detected by a fluorescent probe 2,7-dichlorofluorescein diacetate(DCFH-DA).The mitochondrial membrane potential(Δψ m)in N2a/APP cells was detected by using JC-1 staining method.Immunofluorescence was used to detect the generation of 8-hydroxy-2′-deoxyguanosine(8-OHdG)and 4-hydroxynonenal(4-HNE).RESULTS Quercetin attenuated the enhancement of p-ERK1/2,reductions of p-Akt,and decreased levels of APP expression.More-over,quercetin alleviated loss of mitochondria membrane potential(MMP)since it attenuates these oxidative stress,as reflected in the levels of ROS,4-HNE and 8-OHdG,was elevated in N2a/APP cells and these effects were again ameliorated by quercetin.CONCLUSION Neuroprotection by quercetin in N2a/APP cells involves normalizing the impaired mitochondrial function and reducing oxidative stress via inactivation of the ERK1/2 and activation of the Akt pathways.