The mechanism of Codonopsis pilosula in treating chronic obstructive pulmonary disease via exploring network pharmacology and multi-omics.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Codonopsis pilosula (CP) is a traditional Chinese medicine used to tonify qi and strengthen the spleen, with reported anti-inflammatory effects. However, its efficacy and mechanisms in chronic obstructive pulmonary disease (COPD) remain unclear. AIM OF THE STUDY: The purpose of this study was to systematically investigate the therapeutic efficacy of CP against COPD in rats through an integration of network pharmacology and multi-omics, thereby providing experimental evidence for elucidating the underlying mechanisms through which CP exerts its therapeutic effects on the disease. MATERIALS AND METHODS: CP constituents were identified by UPLC-QTOF-MS. A rat COPD model was induced by cigarette smoke and LPS. Pulmonary function, histopathology, ELISA, RT-qPCR, and Western blot were performed. Network pharmacology, transcriptomics, and metabolomics analyses were used to explore potential mechanisms. RESULTS: A total of 114 compounds were identified. CP improved pulmonary function, reduced inflammatory cell infiltration, and alleviated airway and alveolar injury. Network pharmacology suggested regulation of TNF, IL-1β, NF-κB, MAPK3, and TLR4, mainly through PI3K-Akt, MAPK, and NF-κB pathways. Multi-omics indicated involvement of xenobiotic response, apoptosis regulation, and lipid metabolism, with glycerophospholipid and arachidonic acid metabolism as key processes. Molecular validations supported these findings. CONCLUSION: Codonopsis pilosula enhanced pulmonary function and attenuated airway inflammation in COPD rats, likely through modulation of lipid metabolism and inhibition of the TLR4/MAPK/NF-κB pathway. These results provide pharmacological evidence supporting its traditional use and suggest its potential as a therapeutic agent in COPD management.