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

Abstract

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 in vitro permeation test (IVPT) of SFTOT was conducted using a modified Franz diffusion cell method. Ultra-high-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap/MS) was employed to analyze data from the transdermal receiving solution, enabling comprehensive identification of the components that permeate through the skin. To predict the potential mechanisms by which SFTOT may treat COPD, network pharmacology was used to construct a component-target-collaterals network. Additionally, molecular docking was applied to verify the interactions between the potential transdermal active components of SFTOT and the core targets.

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.

Keywords: Franz diffusion cell; Shufeitie ointment; UHPLC-Q-orbitrap/MS; chronic obstructive pulmonary disease; external preparations; network pharmacology.

Figure 1

SFTOT transdermal component positive ion pattern.

Figure 2

SFTOT transdermal component negative ion pattern.

Figure 3

Inference of fragmentation pathway of luteolin quality spectrum.

Figure 4

Inference of fragmentation pathway of tetrahydropalmatine quality spectrum.

Figure 5

Inference of fragmentation pathway of 6-gingerol quality spectrum.

Figure 6

Venn plot of the intersection between SFTOT and COPD targets.

Figure 7

Core target screening process diagram.

Figure 8

The core targets analyzed by PPI network.

Figure 9

KEGG enrichment analysis of skinpermeable components of SFTOT against COPD (top 20 were listed).

Figure 10

GO enrichment analysis of skinpermeable components of SFTOT against COPD (top 10 were listed). BP, biological process; CC, cellular component; MF, molecular function.

Figure 11

“Component-target-pathway” network model (The hexagon is the component, the blue diamond is the target, and the red inverted triangle is the pathway).

Figure 12

Molecular docking binding energy heat map of targets and active ingredients.

Figure 13

SFTOT core components are interconnected with molecules of core targets. (A) Apigenin and TNF. (B) 7-O-Methylluteolin and ALB. (C) Luteolin and ALB. (D) Luteolin and EGFR. (E) Quercetin and CASP3. (F) Kaempferol and AKT1.