Integrating bioinformatics analysis with molecular simulation to elucidate the therapeutic mechanism of Guizhi Fuling Wan for adenomyosis and endometriosis

To elucidate the mechanism of Guizhi Fuling Wan (GFW) against adenomyosis (AM) and endometriosis (EM) using an integrated approach combining network pharmacology, molecular docking, and molecular dynamics simulation. GFW components and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction databases, while AM and EM targets were obtained from GeneCards and Open Targets Platform. Intersection targets were identified, and a herb-ingredient-target network was constructed. Protein-protein interaction networks, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and molecular docking were performed, followed by 200 ns molecular dynamics simulations. Seventy-six active ingredients and 480 potential GFW targets were identified, with 176 intersecting with AM and EM. Core ingredients included cerevisterol, kaempferol, and baicalein; hub targets comprised AKT1, MAPK3, HSP90AA1, BCL2, TP53, ESR1, and JUN. Enrichment analysis implicated PI3K-Akt, MAPK, focal adhesion, and apoptosis pathways. Molecular docking and dynamics confirmed stable interactions between core ingredients and AKT1. GFW may exert therapeutic effects against AM and EM through a synergistic multi-component, multi-target mechanism involving the neuro-endocrine-immune-metabolic axis and key signaling pathways, which may provide a systems-level rationale for its clinical application.