通脉降糖胶囊防治糖尿病认知障碍的作用及机制研究OA

Objective To elucidate the therapeutic efficacy of Tongmai Jiangtang Capsule(通脉降糖胶囊,TMJTC)against diabetes-associated cognitive decline(DACD)and explore the underlying mechanisms.Methods A diabetic mouse model was established using db/db mice and subsequently treated with TMJTC.Random blood glucose and learning-memory abilities were assessed to evaluate the pharmacological efficacy of TMJTC in DACD.UHPLC-Q-Exactive HFX was employed to identify brain-penetrant active constituents of TMJTC.Putative targets of brain-penetrant compounds were predicted using BATMAN-TCM and BindingDB,while DACD-related tar-gets were collected from GeneCards and OMIM.Intersection targets were obtained using the Venny 2.1.0 platform.Compound-target and protein-protein interaction(PPI)networks were constructed to screen major active constituents and core targets,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses using the DAVID database.Results TMJTC significantly reduced random blood glucose levels and alleviated cognitive impairment in diabetic mice.A total of 58 brain-penetrant compounds were identified,among which Valeric acid,(1S,2R)-2-amino-1-phenylpropan-1-ol,(E)-4-(2,2-dimethyl-6-methylidenecyclohexyl)but-3-en-2-one,1,1,6-trimethyl-2H-naphthalene,and Hexylitaconic acid were the main constituents.A total of 2101 putative targets related to brain-penetrant compounds were obtained,including 1538 DACD-related intersection targets.TP53,AKT1,TNF,SRC,and CTNNB1 were identified as the core targets.KEGG enrichment indicated that TMJTC may exert anti-DACD effects primarily by regulating reactive oxygen species(ROS)-related signaling pathways and advanced glycation end product-receptor(AGE-RAGE)signaling pathways.Conclusion TMJTC may mitigate DACD by targeting TP53,AKT1,TNF,SRC,CTNNB1,and modulating ROS-related signaling pathways and the AGE-RAGE signaling pathway.