Abstract
Background Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with high morbidity and mortality. The conventional therapies remain palliative and have various undesired effects. Shenmai injection (SMI) has shown positive effects on COPD, but its molecular mechanisms are still unclear. This study aims to investigate the bioactive ingredients and underlying mechanisms of SMI in treating COPD based on network pharmacology analysis and molecular docking validation.
Methods Active ingredients in SMI were sourced from the TCMSP, SymMap, and BATMAN-TCM databases, with their targets predicted using Swiss target prediction. Potential COPD targets were obtained from the GeneCards, OMIM and GEO databases. Cytoscape software was employed to construct the candidate component-target network for SMI in treating COPD. Furthermore, the functions and signaling pathways of shared targets between SMI and COPD were enriched by GO and KEGG analyses. Finally, molecular docking studies of key active ingredients and hub targets were performed using Autodock vina software.
Results A total of 28 active components were identified, corresponding to 606 targets, including 341 common targets shared by the active components and COPD. The top 10 hub targets were screened, namely STAT3, SRC, EGFR, HSP90AA1, AKT1, IL6, TNF, BCL2, JUN and CCND1. GO enrichment analysis yielded 127 entries for biological processes (BP), 32 for cellular components (CC), and 33 for molecular functions (MF). The significantly enriched iterms in BP, CC, and MF enrichment were associated with response to xenobiotic stimulus, plasma membrane, and protein serine/threonine/tyrosine kinase activity, respectively. KEGG enrichment analysis identified 189 significantly enriched pathways, primarily including pathways in cancer, PI3K-Akt signaling pathway and chemical carcinogenesis- receptor activation. These pathways play roles in the effect of SMI on treating COPD. Molecular docking results demonstrated the effective binding of the primary active ingredients (Ophiopogonanone A, Ruscogenin, Stigmasterol) to their respective targets (EGFR, AKT1, HSP90AA1).
Conclusion SMI treats COPD through a multi-component, multi-target, and multi-pathway synergistic network, providing a basis for further exploration of SMI's mechanisms in COPD treatment.