Study On The Anti-brain Aging Effect And Mechanism Of Polygonatum Sibiricum Polysaccharide Based On Intestinal Flora And Metabolomic

Objective:The purpose of this study is to investigate the metabolic and intestinal microbial changes of brain aging mice caused by D-galactose(D-gal)based on microbiome and metabolomics techniques,and discussed the delay effect of Polygonatum sibiricum polysaccharides(PSP)from the perspective of microbiota-gut-brain axis.Methods:D-galactose was intraperitoneally injected to create rapid-aging animals.Thirty-six C57BL/6J male mice of 6-week-old were divided into six groups(n=6).The mice in the normal control(NC)group were intraperitoneally injected with normal saline and perfused with distilled water.D-galactose(D-gal)group mice were intraperitoneally injected with D-galactose(150 mg/kg/D)every day for 8 consecutive weeks,and gavaged with distilled water from the fifth week;PSP150,PSP300,and PSP600 group mice were intraperitoneally injected with D-galactose(150 mg/kg/D)every day,and fed 150,300,and 600 mg/kg/D Polygonatum sibiricum polysaccharides,mice in the Donepezil group were intraperitoneally injected with D-galactose(150 mg/kg/D)for 8 consecutive weeks and given 1.2 mg/kg/D donepezil.The MWM water maze test was used to assess mice’s spatial learning and memory ability,HE staining and Nissl staining were used to observe histopathological changes in brain tissue,and ELISA was used to detect the content of MDA and the activities of SOD and GSH-Px in the hippocampal tissue and serum of mice in each group,using 16S rDN A technology to detect intestinal microorganisms and HPLC-QE-MS/MS technology to detect metabolites in feces,serum and cortex.Results:When compared to the normal control group,the D-gal group mice’s learning and memory ability reduced dramatically,and there were varying degrees of recovery after PSP administration,with the PSP600 group mice’s recovery impact being the most significant.Histopathological results showed that the cells in the CA1 and CA3 portions of the hippocampus in the D-gal group were more loosely distributed,with fewer numbers and nuclear pyknosis,compared to the normal control group.After administration,the pathological state of the PSP group and Donepezil group mice was adjusted to normal levels,the neuron cells are densely packed,the morphology is complete,and there is no necrosis.The ELISA results showed that the concentration of MD A in the hippocampus and serum of aged mice increased dramatically following D-gal modeling,whereas the activities of SOD and GSH-Px decreased significantly.The PSP600 group’s content decreased to some amount,while the activities of SOD and GSH-Px increased to varying degrees,with the effect of the PSP600 group reverting to the normal control group being the most noticeable.The 16S rDNA results revealed substantial variations in the composition and structure of the intestinal flora between groups,mainly bacteroidota,firmicutes,actinobacteriota,campilobacterota.HPLC-QE-MS/MS results revealed significant changes in the differential metabolites in feces,serum,and cortex across groups.Differential metabolites were mainly enriched in metabolic pathways such as taurine and hypotaurine metabolism,purine metabolism,alanine,aspartate and glutamate metabolism,glycerophospholipid metabolism and riboflavin metabolism.Conclusion:Polygonatum sibiricum polysaccharides can delay cognitive impairment in aging mice by regulating the micro biota-gut-brain axis,and improve brain tissue lesions and regulate oxidative stress indicators,which may be one of the mechanisms by which Polygonatum sibiricum polysaccharides inhibit brain aging.