Effects Of Gan Mai Da Zao Decoction On Alzheimer’s Disease Rats Based On Metabonomics

Objective:Alzheimer’s disease（AD）is a common neurodegenerative disease with a complicated pathogenesis.At present,there is a lack of markers that can be used for AD diagnosis and drugs that can be used for a long time clinically with little side effects.Traditional Chinese medicine compound Gan Mai Da Zao Decoction（GMDZ）is widely used clinically to treat neurodegenerative diseases,but there are few studies on the treatment of AD.Therefore,this study aims to explore the composition of GMDZ,establish an AD rat model,and explore the mechanism of GMDZ in the treatment of AD based on metabonomics and lipidomics.Methods:Methods:（1）The composition of GMDZ was identified based on UPLC-Q-TOF-MS technology and UINIFI software.（2）Establishment of AD rat model:the AD rat model was established by intragastric Al Cl₃,intraperitoneal injection of D-galactose,and intraventricular injection of Aβ;the MMW water maze test was used to verify the behavior of the model;Western Blot method was used to detect expression of Aβin the hippocampus of the rats.（3）Metabolomics technology based on UPLC-Q-TOF-MS combined with multivariate analysis methods to analyze rat plasma and urine samples.（4）Lipidomics technology based on UPLC-Triple-TOF/MS combined with multivariate analysis to analyze plasma samples.Results:（1）A total of 123 compounds were identified in GMDZ Decoction,there are108 compounds under positive mode conditions;62 compounds under negative mode conditions.（2）In the MWM test,the escape latency of the GMDZ group was significantly lower than that of the AD group,the frequency of passing the platform in the AD group was less than that of the Sham group（p≤0.01）,and the frequency of passing the platform in the AD group was less than that of the GMDZ group（p≤0.01）.（3）When compared the AD group and the Sham group,39 plasma differential metabolites were identified,involved 6 metabolic pathways;33 urine differential metabolites were identified,involved 3 metabolic pathways.When the GMDZ group was compared with the AD group,39 plasma metabolites were identified,involved 5 metabolic pathways;43 urine metabolites were identified,involved 5 metabolic pathways.（4）Under the positive mode conditions,25 lipids changed significantly when the Sham group compared with the AD group,and 24 lipids changed significantly under negative mode conditions.When compared AD group with GMDZ group,20 lipids changed significantly,and 17 lipids changed significantly under negative mode conditions.Conclusion:A total of 123 compounds were identified in Gan Mai Da Zao Decoction,which providing a material basis for quality control and follow-up experiments,and a new perspective for the discovery of new chemical drugs.The potential urine and plasma biomarkers to distinguish Sham group from AD group,and AD group from GMDZ group were determined.Abnormal metabolism in plasma and urine of AD rats was mainly related to amino acid metabolism,fatty acid metabolism,sphingolipid metabolism and glycerophospholipid metabolism.GMDZ can treat and improve AD by regulating amino acid metabolism and lipid metabolism.