Neuroprotective Mechanisms and Metabolomics Analysis of Jiedu Yizhi Formula in Alzheimer's Disease

Abstract

Abstract Aim of the study：We studied the metabolites in the brain tissue of Alzheimer's Disease (AD) transgenic mice to investigate how Jiedu Yizhi Formula (JDYZF) protects against AD and to validate the scientific basis of the prescription using the "Marrow deficiency and toxin damage" theory. Materials and methods: The effect of JDYZF treatment on cognitive dysfunction was evaluated using the Morris water maze test in the APP/PS1 transgenic mouse model. Furthermore, the impact of JDYZF on typical AD pathology was assessed through Hematoxylin-eosin staining. Additionally, the protective effect of JDYZF on AD neurons was studied using Nissl staining. Moreover, potential mechanisms of action were analyzed through LC-MS/MS-based untargeted metabolomics of mouse brain tissue. Results: The administration of JDYZF significantly ameliorated memory deficits and mitigated typical histopathological changes in AD mice. Upon comparison of the differential metabolites between the model control group and the blank control group with those between the JDYZF group and the model control group, 17 endogenous metabolites, including 1-methyluric acid, were found to be significantly different. These differential metabolites were primarily involved in the pathways of caffeine metabolism and glycerophospholipid metabolism. Conclusion: In this study, we have effectively illustrated the neuroprotective effect of JDYZF on AD through experimentation with the APP/PS1 transgenic mouse model. The findings indicate that the utilization of JDYZF can ameliorate the metabolic disruptions in brain tissue and serve as a viable therapeutic intervention for AD.