Study On The Mechanism Of Lycium Barbarum In Delaying Alzheimer’s Disease In C.elegans

Alzheimer’s disease is considered to be an age-related neurodegenerative disease,which is characterized by insidious onset,difficult diagnosis,high mortality and disability rate,and persistent decline in intelligence.Due to the increasing aging of the population,AD also seriously threatens the future medical budget,causing a great economic burden on the society.The pathological characteristics of Alzheimer’s disease are mainly the formation of beta-amyloid plaques and neurofibrillary tangles.However,the pathogenesis is very complex and many aspects remain to be further studied.The drugs currently approved for the treatment of AD are mainly cholinesterase inhibitors,but such drugs cannot reverse,stop or even slow the damage and destruction of neurons.More and more evidences show that oxidative stress is one of the factors causing aging and neurodegenerative diseases.To date,various natural products from different sources have been found to have anti-oxidative stress,anti-aging,anti-tumor and neuroprotective functions.The natural products have the advantages of wide sources,diverse structures,and significant biological activities.Caenorhabditis elegans has been used as a model organism for drug screening due to its small size,short life cycle,transparent body,easy observation,and homologous genes for most human diseases.Therefore,the Aβ model of Caenorhabditis elegans,the CL4176 transgenic nematode strain,was used to screen the natural products in this paper.Besides,the natural product possessed the best effect was selected for in-depth research to explore its mechanism of delaying nematode paralysis.We preliminarily selected eight natural products with antioxidant activity after consulting the data.After drug screening,it was found that 10 mg/m L of Lycium barbarum aqueous extract had the best effect,which could delay the paralysis time of C.elegans by 25.06%.Since Lycium barbarum polysaccharide was one of the most important components of Lycium barbarum,further research on Lycium barbarum polysaccharide was carried out.It was found that the effect of the polysaccharide was not as good as the water extract of Lycium barbarum.All the same,the polysaccharide still had a significant effect on delaying the paralysis of C.elegans,and the optimal concentration was 0.5 mg/m L.It is speculated that a variety of components in Lycium barbarum work together to delay C.elegans paralysis.Then,the administration of Lycium barbarum water extract were found to enhance its anti-paralysis effect only after warming up to 25℃,while administration of Lycium barbarum polysaccharide aqueous solution at different periods can play a role.Besides,both the aqueous extract of Lycium barbarum and the aqueous solution of Lycium barbarum polysaccharide could significantly reduce the expression of Aβ and inhibit the deposition of Aβ in C.elegans.By detecting the level of ROS in the nematodes,it was found that the ROS of the C.elegans in the administration group was significantly reduced.Then,Lycium barbarum water extract and Lycium barbarum polysaccharide aqueous solution were also found to significantly increase the level of SOD-3 depending on DAF-16.As a result,the anti-oxidative stress ability of C.elegans were increased while ROS levels in C.elegans were decreased.In addition,by observing the nuclear translocation of transcription factor DAF-16,it was found that the proportion of DAF-16 into the nucleus was significantly higher in the administration groups.Therefore,it was speculated that the aqueous extract of Lycium barbarum and Lycium barbarum polysaccharide aqueous solution enhanced the nuclear translocation of DAF-16 and the activity of its transcription factors,thereby activating downstream signaling pathways.Then,the expression levels of anti-stress,anti-stress and anti-aging related genes in C.elegans were detected by q PCR.Results showed that jnk-1 was significantly downregulated in both administration groups.Finally,in order to ensure its safety,N2 nematodes were used to test the toxicity of the drug.The results showed that the aqueous extract of Lycium barbarum and Lycium barbarum polysaccharide aqueous solution could play a role in a safe dose.In conclusion,by screened anti-Alzheimer drugs using CL4176 transgenic elegans,we found that Lycium barbarum extract and Lycium barbarum polysaccharide could significantly delay the paralysis time.Further the mechanism were explored: they inhibited the toxicity of Aβ by reducing the expression and deposition of Aβ in nematodes,which may be related to promoting the nuclear translocation of DAF-16.By activating the activity of DAF-16,Lycium barbarum extract and Lycium barbarum polysaccharide increased the expression of its downstream gene sod-3,reduced the level of ROS in C.elegans,and resisted oxidative stress caused by Aβ.In addition,it was speculated that the down-regulation of jnk-1 might also be one of the reasons that Lycium barbarum water extract and Lycium barbarum polysaccharide aqueous solution inhibit the expression and deposition of Aβ.In this study,we not only provide a theoretical basis for clarifying the mechanism of Lycium barbarum’s protective effect on nerves,but also provide a certain theoretical basis for the research and development of new anti-Alzheimer’s disease drugs.