Unraveling the active ingredients and molecular mechanisms of Buyi Xiaozheng decoction against ovarian cancer: An integrative approach combining UHPLC-QE-MS, network pharmacology, molecular docking, dynamics simulations, and experimental verification.

Buyi Xiaozheng decoction (BYXZD) is widely used as an adjunct therapy for ovarian cancer (OC) chemotherapy, effectively inhibiting OC progression. However, its targets and mechanisms remain unclear. This study aimed to identify the active components and clarify the molecular mechanisms of BYXZD in OC treatment using an integrated approach combining UHPLC-QE-MS, network pharmacology, molecular docking, dynamics simulations, and experimental validation METHODS: UHPLC-QE-MS was employed to identify the main components of BYXZD. Targets of BYXZD were predicted using PharmMapper and Swiss target prediction, while OC-related targets were retrieved from GeneCards, OMIM, TTD, and CTD databases. The intersection of these targets was analyzed to identify potential therapeutic targets of BYXZD. An "herb-compound-target" network was constructed using Cytoscape, and protein-protein interactions (PPI) were analyzed via the string database. Functional enrichment analysis (GO and KEGG) was performed using the DAVID database. Molecular docking and dynamics simulations were conducted to evaluate the binding affinity and stability of core components with key targets. In vitro experiments were performed to validate the effects of BYXZD on OC cell migration, invasion, and signaling pathways RESULTS: The main components of BYXZD were identified as atractylenolide II, lithospermic acid, baicalein, and scutellarein. PPI, GO, and KEGG analyses identified AKT1, MAPK1, MAPK3, and PIK3CA as key targets, with the PI3K/AKT and MAPK pathways serving as the primary mechanisms. Molecular docking showed high binding affinity between core components and key targets, and molecular dynamics simulations indicated stable interactions between baicalein/lithospermic acid and MAPK1/PI3CA. In vitro experiments confirmed that BYXZD dose-dependently inhibited OC cell migration and invasion by regulating the PI3K/AKT and MAPK pathways CONCLUSIONS: The integrative approach revealed that BYXZD exerts therapeutic effects on OC through multiple components, multiple targets, and multiple pathways, highlighting its potential as a valuable adjuvant therapy for OC.