| Objective:Currently,the drugs for the treatment of Alzheimer's disease mainly include Cholinesterase inhibitors,N-Methyl-D-Aspartate(NMDA)receptor antagonists,Psychosensitizers,and Antioxidants.However,there are no drugs for the treatment of the primary etiology.My country is rich in resources of traditional Chinese medicine,Chinese medicine possesses the characteristics of multiple ways to target.To evaluate the efficacy and safety of Bushen Yiqi Recipe in the treatment of Alzheimer's disease(AD),Cochrane system was used in this study to provide a basis for experimental research and clinical application.The clinical study of professor's self-designed "Bushen Yiqi Recipe" for the treatment of Alzheimer's disease suggested that the effect was accurate,and further basic tests all showed benign result.The main component of Radix astragali,Cycloastragenol(CAG),was investigated in response to the in vitro blood-brain barrier model mediated by A?,and the mechanism of treating AD with Bushen Yiqi Recipe was studied.Method:1.Using Meta-analysis to evaluate the efficacy and safety of Bushen Yiqi Prescription in the treatment of Alzheimer's disease,searching PubMed,CNKI,CBM,Vip Database,Wanfang Database.The literature was published between 2010 and 2018.Read the title,abstract and the full text of the literature related to the clinical evaluation results of the trial system,analyze and screen,select all relevant literatures that meet the inclusion criteria of the trial,extract valid data,Review Manager 5.3 software was used to conduct Meta analysis of the study results.2.To investigate the protection and possible mechanism of Cycloastragalitol on the injury of a-mediated blood-brain barrier model in vitro:? The optimal concentration of oligomer A?1-42 acting on bend.3 cells and the effective protective effect of Cycloastragalinol were studied by MTT method.? The effects of Cycloastragalinol on the apoptosis of bend.3 cells mediated by oligomer A?1-42 were detected by TUNEL and DAPI staining.?We used FCM(FITC/PI)double staining method to detect the effect of the bEnd.3 induced by oligomer A?1-42 after Cycloastragaliol intervention.?The influence of Cycloastragalinol on the clearance rate of A? in the brain was investigated using the in vitro blood-brain barrier model of monolayer bEnd.3 cells.? Apoptotic proteins(Cyto-C?Bcl-2?Bax?Caspase3?Caspase8)?tight junction proteins(Occludin?Claudin-5?ZO-1)and transporters(LRP-1?P-gp?RAGE)were detected by Western blot.Results:1.This experiment to retrieve a total of 124 articles,according to the row,standard last 9 clinical randomized controlled trials and meta-analysis results showed that Bushen Yiqi Recipe group on the treatment group can obviously improve Alzheimer's patients daily life ability assessment scale(ADL)score,simple mental state(MMSE)score,statistically significant differences before and after the treatment;In terms of safety,6 of the 9 literatures included in this study did not describe the related adverse reactions,2 did not report the adverse reactions,and only 1 reported the adverse reactions.However,there was no statistical significance between the control group and the treatment group.2.The results of MTT assay showed that:(1)When the oligomer A?1-42 with 20?mol·L-1 damaged bEnd.3 cells for 24h,the viability inhibitory rate of A?1-42 to bEnd.3 cells was close to 50%.(2)The Cycloastragenol concentration reach 100 ?mol·L-1 the bEnd.3 cells began to apoptosis.(3)The concentration range of 10-75 ?mol·L-1 significantly improved the damage of cell viability induced by oligomer A?1-42 to bEnd.3 cells;3.Western blot results showed that;When treat by Cycloastragenol the expression of mitochondria-dependent pathways and the death receptor apoptosis pathway activated by oligomer A?1-42 significantly decline,Protein levels of tight junctions between endothelial cells such as ZO-1,Occludin and claudin-5 increased.4.Cycloastragenol can increase the clearance rate of soluble A? across BBB models in vitro,which may be related to the increasing of the expression of P-gp and LRP1 and the decreasing of RAGE.Conclusion:1.At present,the randomized controlled clinical trials included showed that Bushen Yiqi Recipe could improve the situation of Alzheimer's disease.However,due to the limitation of the experimental data of this group,the safety of relevant drugs still needs to be evaluated.2.Cycloastragenol can significantly inhibit the cell apoptosis of bEnd.3 cells induced by oligomer A?1-42.3.Cycloastragalitol can inhibit the apoptosis of bend.3 induced by A 1-42,increase the level of closer-junction protein,and improve the permeability between cells.4.Cycloastragalinol can effectively regulate the transport of A? on vascular endothelial cells to improve the effective clearance rate of brain soluble A?. |
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