| Objective:Alzheimer's disease?AD?is a central nervous system degenerative disease characterized by progressive cognitive dysfunction and behavioral impairment.AD is the most common type of dementia in old age,a chronic neurodegenerative disease.The clinical manifestations are memory impairment,aphasia,apraxia,agnosia,impaired visuospatial ability,impairment of abstract thinking and computational power,personality and behavior change.The aging population in China is becoming more and more serious,and the incidence of AD is gradually increasing,which seriously affects the daily life quality of the elderly.However,no effective treatment has been found.At present,there are generally accepted hypotheses about the pathogenesis of AD including the hypothesis of beta-amyloid waterfall,the hypothesis of tau protein,the hypothesis of neurovascular,the hypothesis of disturbance of cell cycle regulation protein,the hypothesis of oxidative stress,the hypothesis of inflammatory mechanism and the hypothesis of mitochondrial dysfunction.Oxidative stress is involved in the development of AD,promoting deposition of A?and hyperphosphorylation of tau protein,while abnormal A?and tau protein promote the imbalance of redox,thus forming a vicious circle that promotes the initiation and progression of AD.Free radicals produced in oxidative stress can be reduced by the application of drugs that inhibit the oxidative stress response,thus promoting the generation of neurons,the reduction of inflammation,and the alleviation of AD symptoms,which has become a hot and promising approach.Maca?Lepidium meyenii,Maca?is an antioxidant plant.It is an annual or biennial herb of the genus brassicaceae,mostly growing in the alpine ecological zones of Puno and Puna in the southeastern part of Peru.It is native to the andes mountains in South America and ranges from 3500 m to 4500 m above sea level.Also known as beetroot or Peruvian ginseng.In addition to anti-oxidation,maca's pharmacological effects include anti-tumor,improved sexual function,improved fertility,enhanced cellular immunity,and improved free radical metabolism.Many cell signaling pathways are affected by redox imbalance,among which nuclear factor E2-related factor 2?Nrf2?is a key factor in intracellular oxidative stress response,while the neuroprotective effect of Heme oxygenase-1?HO-1?is mainly due to Nrf2-dependent activation.The PI3K/Akt signaling pathway is neuroprotective,and activation of the PI3K/Akt signaling pathway leads to the cascade phosphorylation of Akt and inhibits oxidative damage.Therefore,PI3K/Akt-Nrf2-HO-1 pathway plays an important role in anti-oxidative stress of cells.In this study,the cell model of Alzheimer's disease was used and maca extract was given for intervention to detect oxidative stress related indicators and the expression of PI3K/Akt-Nrf2-HO-1 pathway protein,and to explore the protective effect and mechanism of maca extract on Alzheimer's disease cells.Methods:1.Human neuroblastoma blastoma cells?SH-SY5Y?induced by A?25-35 were used to establish the cell model of Alzheimer's disease.2.SH-SY5Y cells were divided into three groups:Control group,Model group,maca extract administration group?A?+Maca?.The activity of GSH-PX and SOD and the content of MDA were determined by kit.Flow cytometry was used to detect the early apoptosis rate of cells in different groups.3.The expression of PI3K/Akt-Nrf2-HO-1 pathway protein and the change of HO-1 expression after the addition of PI3K inhibitor LY294002 were detected by Western blotting.Results:1.The concentration of A?25-355-35 was 20?mol/L or less,and there was no significant effect on cell survival rate after 24 hours of treatment.2.When the concentration of maca extract was 1250?g/mL or less,there was no significant change in cell survival rate.Compared with the Control group,the activity of the oxidative stress indicators GSH-PX and SOD decreased and MDA content increased in the Model group.Compared with the Model group,the activity of oxidative stress indicators GSH-PX and SOD increased and the content of MDA decreased in the maca group.Compared with the Control group,the flow cytometry detection rate of early apoptosis increased in the Model group;Compared with the Model group,the early apoptosis rate of the maca extract group was decreased.3.After the intervention of maca extract,the expressions of HO-1,Nrf2 and p-Akt were up-regulated,while the expression level of HO-1 decreased after the pretreatment with PI3K inhibitor LY294002.Immunofluorescence showed that intervention with maca extract could promote Nrf2 nuclear shift.Conclusion:1.The treatment of A?25-35 on SH-SY5Y cells can induce oxidative stress.2.Maca extract can reduce the oxidative stress response in Alzheimer's disease cell model,and play a protective effect on oxidative damage.3.Maca extract can activate Nrf2-HO-1and PI3K/Akt pathways,and play a protective role in oxidative damage of Alzheimer's disease cells through Nrf2-HO-1 pathway,and Nrf2-HO-1 is regulated by its upstream signaling channel protein PI3K/Akt. |
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