Exploring the mechanism of guben kechuan granules in the treatment of COPD via network pharmacology, molecular docking and molecular dynamics simulations

Guben Kechuan granules (GBKC) is a traditional Chinese medicine commonly used to treat chronic obstructive pulmonary disease (COPD), but its mechanism of action has not been fully explained. The aim of our study is to analyse the mechanism of GBKC in the treatment of COPD by network pharmacology, molecular docking, molecular dynamics simulations and GeneMANIA-based functional association (GMFA) technology. UPLC-MS/MS technology was used to identify the active ingredients of GBKC, and network pharmacology was used to identify key targets and core signalling pathways. Through molecular docking and molecular dynamics simulations, we investigated the interactions between active ingredients and targets. The innovative GMFA method was introduced to construct the target extension database GMFA-ED, and KEGG enrichment analysis revealed the key pathways of multitarget synergistic regulation. The four main active ingredients of GBKC were identified as luteolin, psoralenol, liquiritigenin, and isoliquiritigenin. Its five key targets were found to be AKT1, TNF, IL6, ACTB, and TP53. GO and KEGG enrichment analyses revealed that these proteins are involved mainly in the HIF-1 signalling pathway, the IL-17 signalling pathway and the PI3K‒Akt signalling pathway. Molecular docking and dynamics simulations revealed stable binding of psoralenol to ACTB/AKT1 and of liquiritigenin to ACTB, which was supported by consistent hydrogen bonding and protein interactions. KEGG enrichment analysis via GMFA-ED revealed newly identified signalling pathways, which not only supported the plausibility of the core targets predicted by NP but also further revealed the potential molecular mechanisms of drug action. Psoralenol, liquiritigenin and other active ingredients in GBKC may play a role in the treatment of COPD by regulating multiple components, multiple targets and multiple pathways.