Elucidating the Analgesic Mechanism of Cyperus rotundus via Network Pharmacology and Molecular Docking

Introduction: Pain is an unpleasant sensory and emotional experience associated with, or resembling actual or potential tissue damage. Cyperus rotundus L. is an important medicinal herb traditionally used for the treatment of pain and inflammation. This study employed a network pharmacology approach combined with molecular docking to explore the molecular mechanism of the analgesic effects of C. rotundus. Method: The chemical constituents of C. rotundus were retrieved, collected, and screened using SwissADME and BATMAN-TCM. In addition, pain-related genes in Homo sapiens were searched and filtered from the databases. Protein-protein interactions (PPI) and Ingredient-Target-Pathway (ITP) network were constructed and analyzed. Finally, molecular docking between ligands and proteins was performed using the ReverseDock tool. Results: A total of 158 phytochemical compounds meeting the requirements were selected, with 635 related target interactions between the active compounds and pain. The analyzed PPI network was associated with 3 437 Biological Processes, 335 Molecular Functions, 213 Cellular Components, and 211 KEGG pathways. Four compounds (nootkatone, mustakone, isomustakone, and 4-oxo-α-ylangene) exhibited strong binding to the proteins PGR, FGFR2, and ESR1, with mustakone showing the strongest binding. These findings suggest that the estrogen signaling pathway initiated from the nucleus, the E2-ER-RAS-ERK pathway, and the FGF-FGFR-RAS-ERK pathway may be potential analgesic mechanisms of C. rotundus. Conclusion: A network pharmacology study combined with molecular docking was conducted to investigate the analgesic effects of C. rotundus. Nootkatone, mustakone, isomustakone, and 4-oxo-α-ylangene were identified as key active compounds, primarily acting through binding to the proteins PGR, FGFR2, and ESR1.