The Protective Effects And Underlying Molecular Mechanisms Of Lutein On The Neural Cells Impairment Induced By Neuroinflammation And Oxidative Stress

With the degree of population ageing worse off continuously,Neurodegenerative disease associated with aging is seriously threatening the health of the elderly,such as Alzheimer’s disease and Parkinson’s disease.The intervention research of neurodegenerative diseases is of great significance to the maintenance of human health.Recently,dietary supplementation with neurotrophic and neuroprotective food components has become a new research direction of interfering neurodegenerative diseases.Lutein is a kind of oxygen carotenoids that exists in some dark fruits and vegetables,which is the most abundant carotenoid in the nervous system.Lutein is of great significance to the nervous system development and maintain normal function.It has been reported that lutein has a potent neuroprotective effect,for example supplementing the appropriate dose of lutein can significantly improve age-related macular degeneration and cognitive decline in the elderly.However,there is still a lack of in-depth study on the neuroprotective effect and molecular mechanism of lutein.In recent years,numerous studies have revealed various pathogenesis of neurodegenerative diseases,which provided potential targets for the intervention of neurodegenerative diseases.The neural cell impairment induced by neuroinflammation and oxidative stress is the key factors in the pathogenesis of neurodegenerative diseases.The protective effects of lutein on neural cells impairment induced by inflammation and oxidative stress have not been reported.Therefore,this research will study the protective effects and underlying molecular mechanisms of lutein on the neural cells impairment induced by neuroinflammation and oxidative stress.The results will provide the theoretical basis for the application of lutein which as a new kind of neuroprotective food component to interfere neurodegenerative diseases.The main research contents are as follows:(1)To study the protective effects and underlying molecular mechanisms of lutein on the neural cell impairment induced by neuroinflammationTo interfere lipopolysaccharide(LPS)-induced inflammatory injury in the neural cells by pretreating with lutein.The results shown that lutein could improve the LPS-induced inflammatory injury in the neural cells.At the same time lutein could significantly inhibit the production of inflammatory factors in LPS-induced neural cells,such as nitric oxide,tumor necrosis factor and interleukin-1β.Moreover,lutein could inhibit the expression of some enzyme associated with inflammation,such as inducible NOS and Cyclooxygenase-2.Further studies have shown that lutein inhibits inflammatory injury in the neural cells by inhibiting some signaling pathways associated with inflammation,such as p38,JNK,Akt-mediated NF-κB nuclear translocation,which might be one of the molecular mechanisms that lutein inhibited LPS-induced inflammatory response.(2)To study the protective effects and underlying molecular mechanisms of lutein by regulating Akt signaling pathway.The research shown that lutein could activate Akt signaling pathway in a time-dependent manner,and further to phosphorylate asparagine endopeptidase(AEP),resulting in inhibiting AEP activation and AEP-induced Tau andα-synuclein neurotoxicity effects.Therefore,activating Akt signaling pathway is an important mechanism of neural protection.Since lutein can activate Akt signaling pathway,so lutein had the potential neuroprotective effect on inhibiting AEP toxicity by activating Akt signaling pathway.(3)To study the protective effects and underlying molecular mechanisms of lutein on the neural cells impairment induced by oxidative stress.The research shown that lutein could outstandingly inhibit the overproduction of reactive oxygen species and oxidative stress in the neural cells.Further studies have shown that MPP~+,Tau andα-synuclein induced oxidative stress could impair neural cells,however the activation of Akt signaling pathway can inhibit oxidative stress induced AEP neurotoxic effects and significantly improve nerve cell impairment.Therefore,activating Akt signaling pathway is a key molecular mechanism to inhibit oxidative stress induced nerve cell impairment.Since lutein can activate Akt signaling pathway,so lutein had the potential neuroprotective effect on inhibiting oxidative stress induced neural cells impairment.(4)To study the molecular mechanism of regulating the REDOX balance in neural cells by lutein mediated-Nrf2.The research shown that lutein could activate ERK1/2 mediated antioxidant defense system related nuclear transcription factor Nrf2 nuclear translocation in the impaired neural cells.Further to increase the expression of antioxidant defense system related enzyme and protein in neural cells,on the one hand,to increase the expression of II phase detoxification enzymes including heme oxygenase 1(HO-1)and quinone oxidoreductase 1(NQO1),on the other hand,to increase the content of glutathione(GSH)and restore the enzymatic activity of glutathione peroxidase(GSH-Px)andγ-glutamyl-cysteine synthetase(γGCS).Finally,to inhibit the neural cells impairment induced by oxidative stress through restoring the REDOX balance in neural cells,which was involved with promoting the antioxidant ability and eliminating the overproduction of reactive oxygen species by lutein in the neural cells.Taking together,the research demonstrated that lutein possess the potent neuroprotective effects on the neural cells impairment induced by neuroinflammation and oxidative stress.Further study have illuminated the underlying molecular mechanisms of the neuroprotective effects of lutein.The research indicated that lutein had great potential to interfere the neurodegenerative diseases.Therefore,this study provided the theoretical foundation for the application of lutein which as a new kind of neuroprotective food component to interfere neurodegenerative diseases.