Network Pharmacology, Molecular Docking and Dynamics Simulation Reveal the Anti-Colitis Mechanism of

Purpose: A combination of bioinformatics methods including network pharmacology, molecular docking and molecular dynamics simulation was utilized to investigate the potential mechanism of Methods: We firstly used network pharmacology to screen out the major active components, targets and pathways. Secondly, the top 5 ingredients and the top 5 targets were docked with molecular docking technology respectively. Thirdly, the two protein-compound complexes with the lowest binding scores were subjected to molecular dynamics simulation (MDs). Results: A total of 15 bioactive compounds and 191 targets were identified, with the top 5 compounds being quercetin, beta-sitosterol, naringenin, stigmasterol and diosgenin, and the top 5 targets being AKT1, IL-6, TNF, TP53 and IL-1β. Predominant enrichment was observed in the PI3K-Akt signaling pathway, TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway and apoptosis. Each set of molecular docking calculations was run 50 times and repeated 3 times for statistical analysis, with results showing that the majority of binding energies were less than -5 kcal/mol, indicating successful docking. Specifically, stigmasterol-TP53 (-9.10 ± 0.07 kcal/mol) and diosgenin-TP53 (-8.80 ± 0.73 kcal/mol) are the two complexes with the lowest binding energies for MDs. According to the MDs, the stig-masterol-TP53 and diosgenin-TP53 complex shows ideal conformational stability and interaction energy. Conclusion: Multiple components of SG may exert therapeutic effects on UC through multiple targets and various signaling pathways. Novelty of this study lies in linking SG compounds to UC-specific targets and confirming stable docking/MDs interactions with TP53. However, further validation through in vivo and in vitro experiments is required to provide reliable evidence for clinical application.