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

A combination of bioinformatics methods including network pharmacology, molecular docking and molecular dynamics simulation was utilized to investigate the potential mechanism of Smilax glabra Roxb. (SG) in the treatment of ulcerative colitis (UC).

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).

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.

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.