Mechanisms Underlying the Therapeutic Effects of JianPiYiFei II Granules in Treating COPD Based on GEO Datasets, Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations

Simple Summary COPD is a lung disease characterized by limited respiratory airflow aggravated with time. JPYF II granules are a traditional Chinese medicine used in the treatment of COPD. However, the main components and potential mechanisms of JPYF II granules are still unclear. The purpose of this study was to elucidate the potential mechanism underlying its ability to treat COPD through network pharmacology, molecular docking, and molecular dynamics simulation techniques. Kaempferol, quercetin, and stigmasterol are the main active compounds in the JPYF II Formula in the treatment of COPD, and AKT1, IL-6, and TNF are potential target proteins for the JPYF II Formula in the treatment of COPD. The potential effective compounds, targets, and related potential molecular mechanisms obtained here provide a reference for follow-up studies on COPD.Abstract Background: JianPiYiFei (JPYF) II granules are a Chinese medicine for the treatment of chronic obstructive pulmonary disease (COPD). However, the main components and underlying mechanisms of JPYF II granules are not well understood. This study aimed to elucidate the potential mechanism of JPYF II granules in the treatment of COPD using network pharmacology, molecular docking, and molecular dynamics simulation techniques. Methods: The active compounds and corresponding protein targets of the JPYF II granules were found using the TCMSP, ETCM, and Uniport databases, and a compound-target network was constructed using Cytoscape3.9.1. The COPD targets were searched for in GEO datasets and the OMIM and GeneCards databases. The intersection between the effective compound-related targets and disease-related targets was obtained, PPI networks were constructed, and GO and KEGG enrichment analyses were performed. Then, molecular docking analysis verified the results obtained using network pharmacology. Finally, the protein-compound complexes obtained from the molecular docking analysis were simulated using molecular dynamics (MD) simulations. Results: The network pharmacological results showed that quercetin, kaempferol, and stigmasterol are the main active compounds in JPYF II granules, and AKT1, IL-6, and TNF are key target proteins. The PI3K/AKT signaling pathway is a potential pathway through which the JPYF II granules affect COPD. The results of the molecular docking analysis suggested that quercetin, kaempferol, and stigmasterol have a good binding affinity with AKT1, IL-6, and TNF. The MD simulation results showed that TNF has a good binding affinity with the compounds. Conclusions: This study identified the effective compounds, targets, and related underlying molecular mechanisms of JPYF II granules in the treatment of COPD through network pharmacology, molecular docking, and MD simulation techniques, which provides a reference for subsequent research on the treatment of COPD.