Exploring the mechanism of Platycladi Cacumen in intervening androgenetic alopecia based on network pharmacology, molecular docking, and molecular dynamics simulation.

As a traditional hair-growth-promoting herb, Platycladi Cacumen (PC) has a long history of folk application in the field of hair loss improvement. Preliminary modern pharmacological studies have suggested that its active components may exert potential effects by regulating hair follicle-related signaling pathways; however, for androgenetic alopecia (AGA), the exact targets and specific regulatory mechanisms of PC remain unelucidated, which provides a direction for research on natural drug-based intervention in AGA. In this study, network pharmacology was employed to predict the active components and core targets of PC. Targets associated with AGA were collected, and the intersection targets between PC and AGA were identified. Subsequently, protein-protein interaction (PPI) analysis, Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the intersection targets to screen out the core targets. Thereafter, molecular docking and molecular dynamics(MD) simulation were conducted to validate the interactions between key active components and core targets. The component-target network diagram included 1044 interaction relationships between 32 components and 439 targets, among which quercetin(160), apigenin(150), myricetin(129), and hinokinin(105) were identified as key components. The disease-target network diagram summarized 410 targets associated with AGA. Through PPI network analysis, key targets such as ESR1(46), BCL2(44), INS(44), AR(42), and STAT3(40) were screened out. The results of GO enrichment analysis and KEGG pathway analysis revealed that PC may exert its effects by regulating the EGFR receptor molecule and pathways including the HIF-1 signaling pathway. Molecular docking results showed that the binding energies of all complexes were less than -5.0 kcal/mol, indicating favorable binding effects. MD simulation results showed that the root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), two-dimensional free energy landscape (FEL-2D), and FEL-3D of the simulation system all remained in an equilibrium state with small fluctuation amplitudes. This result indicated that the molecular system had a stable overall conformation, restricted local residue movement, a compact spatial structure, and stable internal chemical bonds-collectively predicting that the quercetin-STAT3, apigenin-AR, myricetin-STAT3, and hinokinin-AR complexes may exhibit satisfactory binding stability. Collectively, Overall, this study systematically investigated the mechanism of action and potential value of PC leaves in intervening in AGA, providing a solid theoretical basis for the intervention of AGA with PC.