Study On The Role And Mechanism Of Action Of Ganoderma Lucidum Polysaccharides In Improving Cognitive Impairment In Alzheimer’s Disease Based On Modulation Of Inflammation In The Liver-Brain Axis

Taking the rat model of Alzheimer’s disease(AD)as the research object,the role and mechanism of Ganoderma lucidum polysaccharide(GLP-1)in improving cognitive impairment in Alzheimer’s disease was studied based on the regulation of liver-brain axis inflammation.Ganoderma lucidum polysaccharides were isolated and purified,and GLP-1 was selected for administration to AD model rats.Pathological staining of rat tissues,transmission electron microscopy of brain mitochondrial ultrastructure,TUNEL staining of brain tissues and flow cytometry detection of apoptosis in brain tissues showed that GLP-1 could alleviate the apoptosis of hippocampal neurons in AD rats,and its mechanism of action was achieved by regulating the expression of related proteins in the apoptotic pathway.Pathological staining of rat liver and measurement of serum liver function indexes revealed that GLP-1 could alleviate inflammatory cell infiltration,regulate blood ammonia levels and expression levels of pro-inflammatory factors,improve the inflammatory response on the liver-brain axis,and reduce the degree of liver injury.The Morris water maze experiment showed that GLP-1 could improve cognitive impairment in AD rats.The results of Western blot experiments showed that GLP-1 alleviated apoptosis and inflammatory responses in AD rats by regulating related proteins in the mitochondrial apoptosis pathway and p38 MAPK inflammatory pathway.The effects of GLP-1 on cognitive impairment in Alzheimer’s disease and its mechanism were studied by gas chromatogram-mass spectrometry(GC-MS)and metabolomics.The results showed that GLP-1 could regulate the abnormal energy metabolism pathway and make the disturbed metabolism return to the normal level through up-regulation or down-regulation.The 42 biomarkers involved were:Acetoacetic acid,Fumaric acid,Pyroglutamic acid,L-Aspartic acid,Oxoglutaric acid,L-Glutamic acid,L-Methionine,Dopamine,cis-Aconitic acid,N-Acetyl-L-aspartic acid,4-Hydroxyphenylpyruvic acid,L-Tyrosine,Citric acid,L-Lactic acid,Metanephrine,Urea,Glyoxylic acid,L-Arginine,Glycine,Pyruvic acid,L-Alanine,3-Hydroxybutyric acid,Succinic acid,4-Hydroxyproline,Ornithine,Citrulline,2-Ketobutyric acid,Adenine,Spermidine,Cysteinylglycine,Spermine,Glucaric acid,Sphingosine,Hypoxanthine,Indoleacetaldehyde,Phenylpyruvic acid,Quinolinic acid,Hippuric acid,5-Hydroxyindoleacetic acid,L-Tryptophan,Cyclic AMP and Guanosine monophosphate.The mechanism of action is to regulate inflammation induced changes in a total of eight metabolic pathways: Urea cycle,Phenylalanine and tyrosine metabolism,Citric acid cycle,Arginine and proline metabolism,Tyrosine metabolism,Alanine metabolism,Aspartate metabolism,and Malate-aspartate shuttle.This study demonstrates that GLP-1 has a role in regulating the relative levels of endogenous markers of inflammation in the liver-brain axis in AD rats.At the same time,the experimental data from this study also provide data to support the development of GLP-1 to alleviate the clinical symptoms of AD.