Metabolic profile changes of kidney aging and protective effects of Polygonatum sibiricum polysaccharides on D-galactose-induced aging mice

Objective To investigate the metabolic trajectory of kidney aging and the effects of Polygona-tum sibiricum polysaccharides(PSP)against kidney aging in D-galactose(D-gal)-induced ag-ing mice,based on ultra-performance liquid chromatography/Q-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive MS/MS). Methods A total of 36 C57 BL/6J mice were randomly allocated to six groups:control(CON),model(MOD),PSP low-dose(PSP-L),PSP medium-dose(PSP-M),PSP high-dose(PSP-H),and positive drug ascorbic acid(VC)groups.To create models of aging mice,D-gal was in-traperitoneally administered to all other groups of mice except the CON group.After model-ing,the appropriate Chinese medicine[PSP-L:150 mg/(kg·d),PSP-M:300 mg/(kg·d),PSP-H:600 mg/(kg·d)]or positive drug[ascorbic acid,300 mg/(kg·d)]was administered for interven-tion.Key markers of renal function in urine and serum of mice in each group,such as creati-nine(Crea),urea nitrogen(BUN),and uric acid(UA)levels,as well as key indicators of oxida-tive stress in serum and kidney,including superoxide dismutase(SOD),catalase(CAT),mal-ondialdehyde(MDA),and glutathione peroxidase(GSH-Px)were determined to validate the successful establishment of kidney aging models and to estimate the effects of PSP.Hema-toxylin and eosin(HE),periodic acid Schiff(PAS),and β-galactosidase staining were used to assess the renal pathological changes.The metabolic profiles of serum,kidney,and urine samples from CON,MOD,and PSP-H groups were analyzed by UPLC-Q-Exactive MS/MS,and pattern recognition methods were used to outline the metabolic trajectory of kidney ag-ing and to identify the characteristic metabolites. Results Age-related alterations in renal histopathology and impaired renal function in mice were also associated with oxidative stress indicators.Following the injection of PSP[PSP-H:600 mg/(kg·d)],the pathological indices associated with aging were adjusted to normal levels,renal function and oxidative stress were improved in aging mice,and renal pathological dam-age was markedly improved.Meanwhile,the potential biomarkers were identified by UPLC-Q-Exactive MS/MS analysis and were further analyzed to form related metabolic pathways,with P＜0.05 as a threshold.The results showed that purine,sphingolipid,glycerophospho-lipid,tryptophan,and riboflavin metabolisms were the main metabolic pathways associated with aging.After administration of PSP,these pathological indices returned to normal levels,and biomarkers related to the aging process,such as adenosine monophosphate(AMP),tryp-tophan,and 5-hydroxytryptophan,also demonstrated,to some degree,reverse regulation(promoting synthesis). Conclusion Metabolomics methods based on UPLC-Q-Exactive MS/MS and multivariate sta-tistical analysis can be adopted to establish metabolic profiles in aging mice.PSP has been shown to protect against kidney aging by interfering with the purine,sphingolipid,glyc-erophospholipid,tryptophan,and riboflavin metabolisms in the kidney.