二至丸通过调节衰老大鼠粪便特征性代谢物延缓衰老OA

Objective:To investigate the anti-aging effects and underlying mechanisms of Erzhi Wan(二至丸)through fecal metabolomic analysis.Methods:An aging rat model was established via intraperitoneal injection of D-ga-lactose.Rats were randomized into a normal control group,a model control group,and Erzhi Wan groups of 4 g/kg,2 g/kg,and 1 g/kg.After seven weeks of intervention by gavage,cognitive function was evaluated using the Morris water maze.Serum and fecal samples were collected to measure alanine aminotransferase(ALT),aspartate aminotransferase(AST),superoxide dismutase(SOD),and malondialdehyde(MDA)levels via assay kits.Fecal differential metabolites and metabolic pathways were analyzed by ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry(UPLC/Q-TOF-MS).Results:Compared with the normal control group,the model control group showed a significant prolongation in escape latency,a decrease in the number of platform crossings,and an increase in total swim-ming distance.The level of ALT,AST,and MDA in serum was significantly increased,and the SOD level was significant-ly reduced(P＜0.05 or P＜0.01).Compared with the model control group,the Erzhi Wan groups of all doses showed significantly shortened escape latency,increased number of platform crossings,reduced total swimming distance,and de-creased level of ALT,AST,and MDA in serum,and increased SOD activity(P＜0.05 or P＜0.01).Fecal metabolomics showed that 45 differential metabolites were regulated by Erzhi Wan.The level of bile acids,arachidonic acid(AA),oxi-dized lipids,saturated fatty acids,diacylglycerols(DGs),sphingomyelins(SMs),and lysophosphatidylcholines(Ly-soPCs)was downregulated,whereas unsaturated fatty acids(OA)were upregulated.The anti-aging effects might be closely related to the interconversion of arachidonic acid metabolism,glycerophospholipid metabolism,and pentose-glucu-ronic acid.Conclusion:Erzhi Wan effectively improves learning and memory in aging rats,and its anti-aging mechanism may be related to regulating arachidonic acid and glycerophospholipid metabolic pathways.