Mechanism of Curcumin in the Treatment of Oral Ulcers Based on Integrated Pharmacology and in Vitro Cell Experiments

Abstract: Objective To systematically explore the mechanism of curcumin (Cur) in the treatment of oral ulcers (OU) based on integrated pharmacology and in vitro cell experiments. Methods Potential therapeutic targets of Cur were screened using multi-source bioinformatics platforms, and OU-related gene sets were identified via the GeneCards database. The intersection targets of Cur and OU were obtained, and key hub nodes were determined using the STRING database and Cytoscape software. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the intersection targets. Molecular docking verification of core targets was conducted using AutoDock 4.2.6, and 100 ns molecular dynamics simulation of the Cur-AKT1 complex was performed with GROMACS software. Dynamic stability was evaluated by calculating parameters including root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), and the number of hydrogen bonds. Finally, the regulatory effect of Cur on AKT1 and inflammatory factors was verified in lipopolysaccharide (LPS)-induced human gingival fibroblasts (HGFs) in vitro. Results A total of 1 263 Cur targets and 6 645 OU targets were screened, yielding 928 intersection targets. Protein-protein interaction (PPI) network analysis identified 10 core targets, including CASP3, EGFR, and AKT1. GO and KEGG enrichment analyses revealed that these targets were mainly enriched in biological processes such as negative regulation of apoptotic processes, involving signaling pathways including the PI3K/Akt pathway. Molecular dynamics simulation demonstrated favorable thermodynamic convergence and structural compactness of the system; hydrogen bond analysis confirmed stable polar interactions between Cur and the active pocket of AKT1. Additionally, covariance matrix and free energy landscape analyses revealed that Cur stably binds to AKT1 via conformational induced fit, providing structural dynamic evidence for its therapeutic effect on OU. In vitro cell experiments confirmed that Cur effectively inhibited LPS-induced AKT1 phosphorylation, downregulated pro-inflammatory factors, and upregulated anti-inflammatory factor expression (P<0.01). Conclusion Curcumin exhibits excellent binding stability with the key target AKT1, and exerts anti-inflammatory effects to treat OU by inhibiting AKT1 activity, a mechanism that may involve regulation of the PI3K/Akt signaling axis.