Investigation of Uridine in Anti-Aging-Related Diseases Based on Network Pharmacology, Molecular Docking and Cell Experimental Validation
Abstract
There is currently only literature that verifies through in vivo experiments in animals that uridine can increase the metabolic level in mice, lacking research and validation on the anti-aging mechanism of uridine. Using network pharmacology, 83 drug targets and 5758 disease targets were screened out, and 33 common targets between aging-related diseases and the selected uridine were determined, including key proteins (PLA2G2A, ADK, G6PD, and GLA). Ten core targets were screened out from the Protein-Protein Interaction network (TP53, INS, CASP3, MYC, ADA, SERPINE1, SLC2A4, DPP4, G6PD, and TYMS). Molecular docking provided further verification. The CCK-8 experiment demonstrated that uridine has a significant therapeutic effect on D-galactose-induced senescence in HT22, BV2, and PC12 cells. Biochemical index detection results indicated that uridine can reduce the content of Malondialdehyde (MDA) and the enzyme activity of Lactate Dehydrogenase (LDH) in senescent HT22, BV2, and PC12 cells, increase the enzyme activity of Superoxide dismutase (SOD), and lower the expression levels of inflammatory factors IL-1β and TNF-α, thereby reducing the damage to HT22, BV2, and PC12 cells caused by inflammatory factors. This study highlights the potential of uridine as a source of anti-aging activity and suggests that it can be developed into a new drug for treating aging-related diseases.