Chronic obstructive pulmonary disease (
COPD) has been a major public health problem and is still a formidable challenge for clinicians. It is urgent to find new compounds for minimizing the risk of
disease progression and exacerbation especially in the early phase of
COPD. A
traditional Chinese medicine (TCM) formula, Chuan Bei Pi Pa dropping pills (CBPP), was tested in this study to investigate its potential mechanisms in preventing the exacerbation of
COPD. Phosphoproteomics analysis for a
smog stimulated early stage
COPD mice model was employed to detect the underlying molecular mechanisms of CBPP. In addition,
protein-
protein interaction (PPI) and bioinformatics analyses were included to analyze the key
proteins and predict the key bioactive compounds. The results indicated that
peiminine (PEI) target
epidermal growth factor receptor (EGFR) prevented the exacerbation of
COPD by inhibiting the EGFR signaling pathway, and
ursolic acid (UA) can alleviate
inflammation disorders via inhibition of
CASP3 on
mitogen-activated protein kinase (MAPK) signaling pathway. After in vivo and in vitro evaluations, we revealed that PEI from CBPP, as a lead compound, can improve lung function and alleviate
pulmonary fibrosis by acting on the EGFR and MLC2 signaling pathways. Furthermore, the approach described here is an effective way to analyze and identify the bioactive ingredients from a mixture by functional proteomics analysis.