Potential active ingredients and mechanisms of Shufeitie ointment in the treatment of chronic obstructive pulmonary disease by integrating transdermal chemistry and network pharmacology.

Purpose: This study aims to identify the transdermal penetration components of Shufeitie ointment (SFTOT) and investigate the potential active components and mechanisms through which SFTOT exerts its effects on Chronic Obstructive Pulmonary Disease (COPD). Methods: An Results: Using UHPLC-Q-Orbitrap/MS, we identified 129 transdermal permeation components in SFTOT. Network pharmacology analysis revealed 222 common targets between SFTOT and COPD. The primary active components were predicted to be luteolin, kaempferol, quercetin, 7-O-methylluteolin, apigenin, ferulic acid, palmitic acid, inapinic acid, 6-shogaol, and myristic acid. These components were primarily enriched in the AGE-RAGE, TNF, PI3K-Akt, and MAPK signaling pathways. Protein-protein interaction (PPI) analysis identified TNF, ALB, AKT1, EGFR, and CASP3 as core targets. Molecular docking results showed that 72% of component-target interactions had a binding energy of < -5.0 kcal/mol, indicating strong binding activity. Among these, apigenin exhibited the lowest binding energy with EGFR and consistently lower binding energies with other core targets compared to the other components. This suggests that apigenin may play a key role in treatment. Conclusion: High-resolution liquid chromatography-mass spectrometry effectively identified the transdermal penetration components of SFTOT, providing a foundation for further screening of key active compounds. Our findings suggest that SFTOT may alleviate COPD by downregulating TNF, ALB, AKT1, EGFR, and CASP3 while inhibiting inflammatory mediator release through the AGE-RAGE, TNF, PI3K-Akt, and MAPK signaling pathways. These effects may help reduce COPD-related symptom clusters. Notably, apigenin appears to be a crucial bioactive component in the prevention and treatment of COPD.