Active-Ingredient Screening and Synergistic Action Mechanism of Shegan Mixture for Anti-Asthma Effects Based on Network Pharmacology in a Mouse Model of Asthma

Abstract

Background

Shegan Mixture (SGM) is a traditional Chinese medicine that has anti-inflammatory and therapeutic effects on asthma. However, its active ingredients and combined action mechanism have not been fully elucidated so far. The purpose of this study was to screen the effective ingredients and targets and elucidate the synergistic action mechanism of SGM in asthma mice using the network pharmacological approach.

Methods

A mouse model of asthma model was used in this study. Mice were orally administered SGM at three doses for 4 weeks and the effect of SGM on asthma was evaluated. The active ingredients and their targets of SGM were identified by searching databases, such as Traditional Chinese Medicine Systems Pharmacology Database (TCMSP). The main active ingredients were selected with parameters OB and DL. The synergistic action mechanisms of SGM in asthma were studied through key active ingredient-target interaction network and verified using surface plasmon resonance assay (SPR).

Results

SGM exerts anti-asthmatic effects by reducing lung tissue damage and inflammatory factors (IFN-γ, IL-4, IL-5, and IL-13) in asthmatic mice. Twenty ingredients and 45 related proteins were selected as potential nodes using enrichment analysis and network analysis. Inflammation and smooth muscle regulation-related pathways were considered to be the main pharmacological mechanisms of SGM in the treatment of asthma. Especially, 5 molecule-target pairs (including 3 ingredients and 4 proteins) were well docked with each other and the SPR assay revealed that glabridin-PTGS2 had good binding with 44.5 μM Kd value.

Conclusion

SGM exerts the synergistic anti-asthma effects by virtue of reducing lung-tissue damage and inflammatory factors in asthmatic mice, which explains the theoretical basis for the traditional Chinese medicine, SGM, to treat asthma. Our study thus sheds light on a variety of options including Chinese medicine that could potentially be used in the clinical treatment of asthma.

Keywords:

• Shegan mixture
• asthma
• network pharmacology
• surface plasmon resonance
• traditional Chinese medicine

Acknowledgments

This project was supported by grant from Natural Science Foundation of Shanghai (16401900500) and National Natural Science Foundation of China (81973504).

Abbreviations

SGM, Shegan mixture; TCM, Traditional Chinese medicine; TCMSP, Traditional Chinese Medicine Systems Pharmacology; OB, Oral bioavailability; DL, Drug-likeness; SPR, Surface plasmon resonance; DEGs, Differentially expressed genes; PPI, Protein-protein interaction; GO, Gene ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; IFN-γ, Interferon gamma; IL, Interleukin; ICSs, Inhaled corticosteroids; ELISA, Enzyme-linked immunosorbent assay; SPF, Specific pathogen free; OVA, Ovalbumin; i.p., Intraperitoneal injection; HBSS, Hanks’ balanced salt solution; COX, Cyclooxygenase; LOX, Lipoxygenase; PDB, Protein Data Bank; DXM, Dexamethasone.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted.

Disclosure

The authors declare no conflicts of interest in this work.