Unveiling the therapeutic mechanisms of Yuehua Pill against multidrug-resistant tuberculosis via network pharmacology and molecular docking

Introduction Multidrug-resistant tuberculosis (MDR-TB) presents a severe global health challenge due to limited treatment options. Yuehua Pill, a traditional Chinese medicine formula, has shown clinical efficacy as an adjunctive therapy. However, its molecular mechanisms remain unclear. This study aimed to elucidate the therapeutic mechanisms of Yuehua Pill against MDR-TB using an integrated network pharmacology and molecular docking approach. Methods Active compounds in Yuehua Pill were identified from the TCMSP database. Potential targets were predicted using SwissTargetPrediction and cross-referenced with MDR-TB-related genes from public databases to identify common targets. A protein-protein interaction (PPI) network was constructed using STRING and visualized in Cytoscape to identify hub genes. Functional enrichment analysis was performed to reveal key pathways. Finally, AutoDock Vina was used for molecular docking simulations to validate the binding between key compounds and hub proteins. Results We identified 121 common targets linking Yuehua Pill to MDR-TB. The PPI network analysis pinpointed ten hub genes, including AKT1, IL6, and TNF. Enrichment analyses revealed that these targets are primarily involved in immune responses and inflammatory signaling pathways, such as the HIF-1 and PI3K-Akt pathways. Molecular docking confirmed that key active compounds, notably quercetin and diosgenin, exhibited strong binding affinities to the hub proteins AKT1, TNF, and IL6. Discussion Yuehua Pill likely exerts therapeutic effects via a multi-component, multi-target mechanism, potentially modulating host immune responses and targeting bacterial survival pathways to overcome drug resistance. While offering a scientific rationale for its clinical use, these findings require further experimental validation.