Protective Effect Of Rehmannia Glutinosa On Blood-Brain Barrier In APP/PS1 Mice And Clinical Application Of Chinese Herbal Compound With Rehmannia Glutinosa As Monarch In The Treatment Of Alzheimer’s Disease

ObjectiveAlzheimer’s disease(AD),also known as Senile dementia,is a neurodegenerative disease characterized by progressive cognitive impairment and personality changes,and is the most common type of dementia in the elderly.The pathogenesis of AD is complex,and the exact pathogenesis of AD is still unclear up to now.Drugs for AD are mainly symptomatic treatment,which cannot completely prevent the development of the disease.Moreover,due to factors such as slow onset,single target,heavy economic burden and large side effects,the therapeutic effect is not ideal.Alzheimer’s disease has become an important issue related to human public health,so it is urgent to find a safe and effective drug to treat AD.Chinese traditional medicine has the characteristics of simple and efficient treatment of diseases,and has the advantages of multiple targets,small side effects,so the study of traditional Chinese medicine treatment of AD has become a feasible method.The traditional Chinese medicine rehmannia glutinosa was first recorded in Shennong Materia Medica Classic and listed as top grade.Previous studies by Prof.Yu Guran’s team found that both Rehmannia glutinosa and catalpa,which is main component,inhibit cell apoptosis and effectively protect the integrity of BBB in vitro,but the mechanism of BBB protection in vivo has not been further explored.Therefore,in this study,the internationally recognized APP/PS1 double transgenic mice were used as animal models to explore the effects of Rehmannia glutinosa on behavior and the mechanism of BBB protection in vivo In order to clarify the clinical effect of rehmannia glutinosa in the treatment of AD,the Cochrane systematic evaluation was applied in this study to analyze the compound of rehmannia glutinosa as a monarch medicine,and to further clarify the safety and effectiveness of rehmannia glutinosa as a monarch medicine in the treatment of AD.At the same time,the clinical efficacy of "Bushen Yijing " in the treatment of early AD was observed and studied.The prescription is discussed in detail to provide a useful idea and method for the treatment of AD with Traditional Chinese medicine.Method1.To explore the behavioral effects of Rehmannia glutinosa on APP/PS1 mice and the protective mechanism of BBB.APP/PS1 mice were randomly divided into model group(0.9%NaCl),rehmannia glutinosa low-dose group(5g/kg/d)and rehmannia glutinosa high-dose group(12g/kg/d),and normal wild-type B6C3F1 mice were used as control group(0.9%NaCl).After 3 months of continuous intragastric administration,Nesting behavior test,Rotarod test,Fear conditioning test and Water maze test were performed.After behavioral experiment,thioflavine-T fluorometry staining and immunofluorescence double-standard staining of CD34 and Fibrinogen were performed to compare the deposition of amyloid plaques in cortex and hippocampus and the integrity and exudation of BBB in each group.Finally,protein imprinting method was used to detect the expression levels of tight junction protein Occludin and ZO-1 in cortex and hippocampus of each group of mice.2、To evaluate the efficacy and safety of rehmannia glutinosa compound in the treatment of Alzheimer’s disease.The relevant clinical studies on the treatment of AD by Chinese herbal compound with rehmannia glutinosa as monarch medicine were comprehensively searched in these 8 databases:China National Knowledge Infrastructure Database(CNKI),Wanfang Data,VIP Chinese Science and Technology Full text Database,China Biomedical Literature Database(CBM),Pubmed database,Cochrane Library,EMBASE Pharmaceutical Database,Web of Science database.3.To observe the clinical efficacy of "Bushen Yijing Fang" in the treatment of early AD,and discuss the prescription’s significance and clinical treatment experience,which provides a beneficial idea and method for the treatment of senile dementia with Traditional Chinese medicine.Results1.Animal experimental results suggest that Rehmannia glutinosa can improve APP/PS1 mice behavior and cognition and memory ability;It can significantly reduce the number and area proportion of senile plaques in APP/PS1 mice brain,and reduce the deposition of Aβ in brain.It can protect the integrity of BBB,reduce BBB permeability,improve the expression levels of tight junction protein Occludin and ZO-1,and maintain BBB function.2.A total of 538 patients were included in 7 randomized controlled trials in this meta-analysis.The results showed that the traditional Chinese medicine compound with rehmannia glutinosa as the monarch medicine may improve the cognitive function and daily living ability of AD patients,and has a certain effect on improving the clinical symptoms of AD compared with conventional treatment.No obvious adverse reactions were observed in the treatment of AD by Chinese herbal compound with rehmannia glutinosa.3.By observing the clinical efficacy of "Bushen Yijing fang" in the treatment of early AD patients,the ADAS-Cog score,TCM syndrome score and DSST score of patients treated with Traditional Chinese medicine decreased after 12 weeks.In blank control group,ADAS-Cog score increased,DSST score decreased,and TCM syndrome score increased after 12 weeks.After intervention,the ADAS-Cog score and ADCS-CGIC score of the Traditional Chinese medicine group were lower than those of the blank control group,and the DSST score was higher,while the TCM syndrome score was lower.The results showed that "Bushen Yijing fang"could significantly improve the cognitive function and TCM syndromes of early AD patients.Conclusion1.Rehmannia glutinosa can effectively improve the learning and memory ability of APP/PS1 mice,promote the deposition of Aβ in the brain,protect the integrity of vascular endothelial,reduce the permeability of BBB,and protect the structure and function of BBB.2.The Traditional Chinese medicine compound with rehmannia glutinosa as the monarch medicine has certain advantages in the clinical efficacy of AD,and provides certain evidence-based medical evidence for the treatment of AD by Traditional Chinese medicine,which is of value and significance for further research.However,the articles included in this analysis are all domestic studies,and the quality of quality evaluation is generally not high,so there are still some limitations.Large-scale multi-center randomized controlled experiments and basic theoretical studies are still needed.3.Professor Yu Guran’s "Bushen Yijing fang" with rehmannia glutinosa as monarch medicine can significantly improve the cognitive function and TCM syndromes of patients with early AD,which preliminarily verified the effectiveness of "Bushen Yijing fang" in the treatment of patients with early AD,providing a beneficial method and idea for the application of TCM in the treatment of early AD in the future.