Study On Inhibition Effects Of Three Food-Derived Extracts To Aβ Toxic Aggregates And Oxidic Species

Alzheimer disease(AD)is a commonly found neurodegenerative disease in the elderly population.The main clinical symptoms of patients are memory loss,decreased behavioral ability and changes in patient temperament.The pathological symptoms are a large number of senile plaque deposits around the nerve cells in the hippocampus,deposition of a large number of metal ions,tangles of intracellular nerve fibers,and massive loss of neurons.Recently,studies have shown that the main components of AD in elderly patients with erythema are P-armyloid polypeptide(AP)and large concentrations of copper ions(Cu2+).Aβ induced apoptosis of neurons through two ways.Firstly,the oligomers and fibers formed by aggregation of Aβ in the brain have toxic effects on neurons in the brain.Secondly,Aβ-metal complex produce a large amount of free radicals in the brain through Fenton reaction.when the large-area apoptosis of neurons occurs,which caused by oxidative damage and cytotoxicity caused of Aβ aggregates,the living neurons in the brain cannot complete the normal function of the human body.The brain is in a decompensated period of function at that stage,which eventually leads to the occurrence of AD disease.In this paper,three food resource extracts(Rice bran ethanol extract,RBEE;Malva chloride pigment-3-O-galactoside,Ma-3-gal-Cl;and ginger heptanone extract,5-hydroxy-7-(4’-hydroxy-3’methoxyphenyl)-1-phenyl-3-heptanone,HPH)were selected for their effects on antioxidant damage and inhibition of AP toxic aggregates formation.Thiazolyl blue(3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-Tetrazolium bromide,MTT)experiment,Coumarin-3-carboxylic acid(CCA)experiment,DCFH-DA(2-7-dichlorohydrofluorescein ethylene glycol)experiment,JC-1 experiment,Western blot(WB),Thioflavin T(ThT)experiment and Atomic Force Microscopy(AFM)experiment were employed for investigating the anti-oxidation and Aβ toxic aggregates formation inhibition effects of the food resource extracts.The research findings of this paper are as follows:1.Ultra Performance Liquid Chromatography(UPLC)is used to analyze the main components of RBEE.The results showed that the highest concentration compounds were phenolic acids substances,of which ferulic acid has the highest proportion,with a concentration of 11.77%.MTT and flow cytometry experiments were employed for studying the inhibition effect of RBEE to cell apoptosis which induced by oxidative damage.CCA,DCFH-DA,JC-1,ThT,AFM and WB experiments results indicated that RBEE inhibits cell apoptosis by reducing the amount of hydroxyl radicals and endogenous reactive oxygen species in cells,maintaining mitochondrial membrane potential stability,inhibiting Aβ toxic aggregate formation,and down-regulating the express of caspase-8(pro),caspase-3(cleaved),caspase-9(cleaved),PARP(cleaved)protease,which related with the cell apoptosis pathway.In addition,the results of water maze positioning voyage and spatial exploration experiments indicated that RBEE can improve learning ability of dementia mice which induced by D-galactose.2.The results of MTT and flow cytometry experiments indicated that Ma-3-gal-Cl could inhibit the cell apoptosis which caused by oxidative damage.CCA,DCFH-DA,JC-1,ThT,AFM and WB results indicated that Ma-3-gal-Cl inhibits cell apoptosis by reducing the amount of hydroxyl radicals and endogenous reactive oxygen species,maintaining mitochondrial membrane potential stability,inhibiting Aβtoxic aggregate formation,and down-regulating the express of caspase-3(cleaved)which related to caspase signaling pathway and P-p38 protease in MAPK cell pathway.3.The results of MTT and flow cytometry experiments indicated that HPH could inhibit the cell apoptosis which caused by oxidative damage.CCA,DCFH-DA,JC-1,ThT,AFM and WB results indicated that HPH inhibits cell apoptosis by reducing the amount of hydroxyl radicals and endogenous reactive oxygen species,maintaining mitochondrial membrane potential stability,inhibiting Aβ toxic aggregate formation,and down-regulating the express of caspase-3(cleaved)which related to caspase signaling pathway and P-p38 protease in MAPK cell pathway.In conclusion,food-derived extracts are derived from edible plants,which have the advantages of high safety,plenty sources and high economic benefits.This paper investigated the protection effect of three specific food resource extracts to AD model mice and cells,and the possible mechanism was also explored.The results of this paper will provide important theoretical reference for researchers to explore how to delay the course of AD disease,and provide new ideas for how to make better use of food-borne plants with biological activity.