Network Pharmacology and Molecular Dynamics Identified Potential Androgen Receptor-Targeted Metabolites in Crocus alatavicus

The objective of this study is to identify the active components of <i>Crocus alatavicus</i> and potential targets through a combination of network pharmacology, molecular docking technology combined with molecular dynamics simulation, and binding free energy analyses. A total of 253 active ingredients from <i>C. alatavicus</i> were screened, and 1360 associated targets were predicted through systematic searches conducted using TCMSP, SwissDrugDesign, and SymMap, which were integrated to construct a pharmacological network to dissect the relationships among active components, targets, diseases, and pathways; we found prostate cancer-related genes were significantly enriched among the targets. Subsequently, the core prostate cancer-related targets were identified in the network, and the binding interactions between protein targets and active components were evaluated using molecular docking technology. Furthermore, molecular dynamics simulation and binding free energy analyses were performed to verify the binding stability of the most promising complex. Then, protein-protein interaction network analysis was conducted to evaluate the core target sites, leading to the identification of nine target proteins with significant correlations, providing potential targets for cancer treatment. Furthermore, these targets were found to be associated with 20 signaling pathways, including neuroactive ligand-receptor interactions, prostate cancer, lipid metabolism and atherosclerosis, as well as calcium signaling pathways. The active component-target-disease-pathway network diagram suggests that Capillarisin, Eugenol, 1-(4-Methoxyphenyl)-1-propanol, 2,4,2',4'-tetrahydroxy-3'-prenylchalcone, and 4-Hydroxymandelonitrile may serve as key components targeting prostate cancer. Molecular docking analyses demonstrated that Capillarisin has a high affinity for the androgen receptor (AR), and molecular dynamics simulation was performed to further verify the binding stability, indicating that Capillarisin may exert its pharmacological effects in prostate cancer. Based on the integrated strategies of network pharmacology, molecular docking, molecular dynamics simulation, and binding free energy analysis, this study generated novel insights into the active components of <i>C. alatavicus</i> and potential targets related to prostate cancer, thus providing valuable biological resources for future drug research and development.