Unraveling the mechanism of curcumin in coronary slow flow phenomenon through network pharmacology and molecular docking.

The coronary slow flow phenomenon (CSFP) is associated with an increased risk of adverse cardiovascular events, yet standardized treatment is lacking. Curcumin, a natural compound, has shown potential in alleviating angina and improving metabolic risk factors in CSFP, but its underlying molecular mechanisms remain unclear. This study employed an integrated computational strategy. Network pharmacology was used to identify potential targets of curcumin and CSFP from public databases, and common targets were identified. Functional enrichment analysis was performed on the common targets, and a protein-protein interaction network was constructed. Core targets were identified using MCODE and CytoHubba plugins in Cytoscape. Molecular docking evaluated the binding modes and affinities of curcumin with the core targets, while molecular dynamics simulations and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) calculations validated the stability and binding free energies of the complexes. A total of 120 predicted targets of curcumin and 435 CSFP-related targets were identified, yielding 19 common targets. Functional enrichment analysis revealed that curcumin may treat CSFP by modulating inflammatory response, vascular function, cell migration, proliferation, apoptosis, and oxidative stress. These targets were associated with key signaling pathways, including NF-κB, TNF, and HIF-1. Network analysis and topological algorithms identified five core targets: EGFR, ICAM1, NFKB1, PTGS2, and STAT3. Molecular docking results demonstrated that curcumin exhibited excellent binding affinity with all core targets. Molecular dynamics simulations confirmed that the curcumin-core target complexes remained structurally stable during the 100 ns simulation, and MM/GBSA calculations indicated significantly negative binding free energies, suggesting strong binding driving forces. Curcumin may exert therapeutic effects on CSFP through a multi-target mechanism, primarily by interacting with key proteins including EGFR, ICAM1, NFKB1, PTGS2, and STAT3, thereby regulating the NF-κB, TNF, and HIF-1 signaling pathways. This study provides a theoretical foundation for the application of curcumin in CSFP treatment, though further experimental validation is required.