Mechanism of Shao Kuiling Decoction in Treating Ulcerative Colitis: A Network Pharmacology and Molecular Docking Study.
TL;DR
SKD may exert therapeutic effects in UC through coordinated modulation of multiple targets and pathways involved in inflammation and epithelial repair through a multi-component, multi-target mechanism involving AKT1/TNF/TP53-associated networks and PI3K-Akt/MAPK signaling.
Abstract
Objective
Shao Kuiling Decoction (SKD) is used in the long-term management of Ulcerative Colitis (UC), but its molecular basis remains unclear. Because SKD is a multicomponent formula, a computational approach is useful for identifying candidate compounds, targets, and pathways for further validation.
Methods
Active compounds in SKD were screened from TCMSP using oral bioavailability and drug-likeness criteria. Putative targets were predicted and intersected with UC-related targets. Shared targets were analyzed by protein-protein interaction network construction, GO/KEGG enrichment, molecular docking, and 100 ns molecular dynamics simulations.
Results
A total of 145 active compounds and 94 shared SKD-UC targets were identified. AKT1, TNF, and TP53 were the main hub targets, and the PI3K-Akt and MAPK pathways were the most enriched. Molecular docking showed favorable binding of the major compounds to core targets, with kaempferol‑TNF showing the strongest binding energy of -8.9 kcal/mol and β‑sitosterol‑AKT1 showing -8.4 kcal/mol. Molecular dynamics simulations revealed that the kaempferol‑TNF and β‑sitosterol‑AKT1 complexes remained stable over 100 ns, with RMSD values plateauing at 0.20-0.25 nm and 0.15-0.20 nm, respectively, and maintained consistent hydrogen bonding. In contrast, the acacetin‑TP53 complex showed greater fluctuations, indicating weaker stability.
Discussion
These findings suggest that SKD may exert therapeutic effects in UC through coordinated modulation of multiple targets and pathways involved in inflammation and epithelial repair. In a broader context, this study provides a systems-level basis for understanding the potential mechanism of SKD in UC and offers focused directions for future experimental validation.
Conclusion
SKD may exert anti-UC effects through a multi-component, multi-target mechanism involving AKT1/TNF/TP53-associated networks and PI3K-Akt/MAPK signaling.