Verification of the mechanism of uridine in promoting neural regeneration via network pharmacology and molecular docking

JOURNAL/rmrep/04.03/02273995-990000000-00028/figure1/v/2026-02-16T213014Z/r/image-tiff Uridine is a glycosylated pyrimidine analog formed by the connection of uracil and ribose rings, which can increase the level of phosphatidylcholine in the brain and is beneficial for neural recovery. This study aimed to reveal the structure-activity relationship of uridine in promoting neural regeneration and to explore its underlying mechanism using network pharmacology and molecular docking methods. Through network pharmacology, 83 drug targets and 4811 disease targets were predicted, and 37 common targets between neural regeneration and selected uridine were identified, including key proteins such as TP53, INS, CASP3, TYMP, NES, HEXB, and MYC. Three core targets, TP53, INS, and CASP3, were selected from the protein-protein interaction network. Gene Ontology enrichment analysis indicated that the mechanisms by which uridine promotes neural regeneration are related to nucleoside metabolic processes, regulation of neuronal apoptosis, nucleoside monophosphate biosynthesis, and leukocyte apoptosis. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the mechanisms by which uridine promotes neural regeneration are associated with neuroactive ligand-receptor interaction, p53 signaling pathway, colorectal cancer, small cell lung cancer, pyrimidine metabolism, human cytomegalovirus infection, hepatitis B, apoptosis, PI3K-Akt signaling pathway, and nucleotide metabolism. Molecular docking results showed that the binding energies of uridine with the three core targets TP53, INS, and CASP3 were all below –2.5 kcal/mol, indicating good docking activity. Among them, uridine exhibited the strongest binding with TP53 and the weakest with INS. These findings indicate that uridine exerts its regenerative effects through multi-target regulation and multi-pathway intervention, providing an innovative theoretical basis for its application in neural regeneration.