The Research Of Alzheimer’s Disease Alleviated By Curculigoside Through Regulating Mitochondrial Stress

Curculigoside（CCG）,a phenolic glycoside active substance,was extracted and recrystallized from the rhizome of Curculigo orchioides Gaertn by ultrasound-assisted organic solvent extraction.As Curculigo orchioides Gaertn has a long history of traditional Chinese medicine for kidney Yang deficiency,internal typhoid disease such as the virtual.As for osteoporosis conditions,myocardial ischemia/reperfusion and nerve injury,its extractive,CCG in the modern pharmacology study shows that has certain therapeutic effect.By its own anti-inflammatory and anti-oxidant effects,CCG can protect the cells damaged by oxidation.In particular,the scavenging effect on free radicals,as an antioxidant,CCG plays a good protective role on neurons in alleviating oxidative damage and reducing cell apoptosis.AD,characterized by full-scale dementia,is a heterogeneous disease in which psychological and physiological changes can become the inducement,and the specific pathogenesis has not been fully elaborated.Current mainstream theories focus on the deposition ofβ-amyloid protein（Aβ）and the formation of neuronal tangles resulting from the hyperphosphorylation of Tau.The neurotoxicity of Aβis mainly reflected in the stimulation of free radical production,triggering mitochondrial dysfunction,activation of oxidative stress,and ultimately leading to the loss of a large number of neurons.Tau protein has a synergistic effect with Aβ,participating in Aβinduced memory damage,neuron hyperexcitability and other processes.Under normal circumstances,glutamate（Glu）,as an excitatory transmitter,participates in the physiological process of the central nervous system.When Glu accumulates in high concentrations,it becomes a neurotoxin and is present in neurodegenerative diseases.In AD,the presence of large amounts of Glu leads to calcium overload,which leads to energy expenditure,and ultimately to mitochondrial failure and mitochondrial stress.HT22 treated with L-Glu has a good application as a Glu destruction model to explore cellular physiological processes such as oxidative stress.B6C3-TG（App SWEPSEN1 DE9）/NJU（APP/PS1）double transgenic model mice,which can express the mutant human presenilin protein（DELTAE9）and human mouse amyloid preprotein（APPswe）fusion,are ideal AD model animals based on the pathogenesis hypothesis of AD.In this study,the in vitro model used the mouse hippocampal neuronal cell lines destroyed by excessive Glu to discuss the protective effect of CCG on neurons by regulating mitochondrial stress and oxidative stress.CCG maintains mitochondrial homeostasis,thereby inhibiting mitochondrial dysfunction caused by mitochondrial stress and oxidative stress damage caused by excess reactive oxygen species.In APP/PS1 mice,Aβ_1-42 accumulation due to a genetic mutation was reduced after CCG treatment and cognitive impairment was improved.The experimental results indicate that CCG protects mitochondrial integrity by maintaining normal mitochondrial membrane potential,controlling calcium overload and reducing the generation of oxygen free radicals,thereby reducing mitochondrial stress and oxidative stress damage caused by L-Glu treated HT22.Meanwhile,in APP/PS1 mice,CCG reduced plaque deposition and neural tangles,and regulated the expression of neurotransmitters and related biological enzymes,which may be a mechanism for alleviating cognitive impairment.Through proteomic screening,CCG can further reduce the damage of neurons caused by stress through Nrf2 and its downstream antioxidant factors,AMPK pathway and apoptotic factors.To sum up,this study system proves that the CCG characteristics of AD pathology relief,combining immune enzyme technology,immunohistochemical and proteomics,explore the CCG by mitochondrial stress means a potential target for the treatment of AD,for traditional Chinese medicine extract CCG become effective for the treatment of AD phenolic glycosides active material provides experimental data and theoretical basis.