Study On The Alleviate Alzheimer’s Disease Mechanism Of Aqueous Extract And Polysacharin In Astragalus Mongholicus In C. Elegans

Alzheimer’s disease is an age-related neurodegenerative disease and the most common cause of dementia.This is an increasingly serious global health problem that places a huge economic burden on individuals and society.Due to the unknown etiology and pathogenesis of AD,there is no specific treatment method.The drugs currently used for AD are mainly cholinesterase inhibitors,but they cannot cure AD.It is hoped that symptomatic interventions can prolong the period of relative health rather than pain.Therefore,there is an urgent need to develop drugs or treatments to alleviate the symptoms of patients,or it may delay and prevent the disease from continuing to develop,or reduce the chance of disease.For this reason,scientists all over the world are working for itA large number of studies have shown that natural products have anti-oxidant,anti-stress,anti-inflammatory,anti-depressant,anti-anxiety,anti-fatigue,and sleep promotion effects,these effects suggest that our natural products may have a role in the treatment of AD.The natural properties of natural products make it safer,produce fewer side effects,and are more suitable for complex diseases.Therefore,this paper screens natural products.The etiology and pathogenesis of AD are still being studied,but there are several representative hypotheses that are widely accepted,especially the 3-amyloid(Aβ)accumulation hypothesis.It is believed that the imbalance between the production and degradation of Aβ causes an excessive accumulation and deposition of Aβ in the brain,which leads to the cascade of inflammation,neurofibrillary tangles,axonal damage and synaptic loss,leading to neuronal apoptosis and dementia.In this article,Aβ transgenic C.elegans CL4176 was used as a drug screening model to screen for drugs against AD based on the Aβ hypothesisMost natural products have a good effect in delaying the paralysis of CL4176 nematodes.In this paper,Astragalus with the best effect is selected as the research object.A validated and effective Zijuan Pu’er tea water was used as a positive control Astragalus extracts with drug concentrations of 1 mg/mL,5 mg/mL,and 10 mg/mL all had an effect on delaying paralysis and delaying paralysis.Depending on the concentration,5mg/mL astragalus extract was selected for subsequent studies.The effects of astragalus polysaccharides,which are components of astragalus,were investigated.It was found that although astragalus polysaccharides alone are not as effective as astragalus,they also have a role in delaying paralysis.Among them,0.5 mg/mL Astragalus polysaccharide aqueous solution was the bestFirst,the toxicity of the drug was tested,and it was proved that the astragalus extract and astragalus polysaccharide aqueous solution can work at a safe dose Secondly,the levels of Astragalus extract and Astragalus polysaccharide aqueous solution were tested,and it was found that it reduced the level of Aβ mRNA in CL4176 nematodes and inhibited the deposition of Aβ,which indicates that the drug may be acting before transcription.After pretreatment of the nematodes,it was found that the paralysis of the nematodes could still be delayed.The mRNA expression level of anti-aging related genes in nematodes was detected,and the sod-3 gene was significantly down-regulated.Then,in order to investigate whether the anti-oxidative stress ability of nematodes is strengthened,it is experimentally concluded that astragalus water extract and astragalus polysaccharide aqueous solution can reduce the level of ROS in nematodes and increase SOD activity in nematodes.To further verify the anti-stress mechanism,TJ356 nematodes were used to observe the localization of DAF-16 in C.elegans,and the proportion of DAF-16 entering the nucleus in the experimental group was increased.Using the nematodes co-expressed with SOD-3::GFP to confirm administration,DAF-16 in the experimental group played a role after transcription,which improved the ability of the nematodes to resist oxidative stress.In conclusion,this paper screens drugs for AD through Aβ transgenic C.elegans,and further explores the mechanism of drug delaying paralysis:Astragalus extract and astragalus polysaccharide aqueous solution can inhibit Aβ toxicity and significantly delay paralysis of nematodes,which may be related to inhibiting Aβ deposition and improving the ability of the nematodes to resist oxidative stress caused by Aβ.