A systematic pharmacological strategy-based to decode the synergistic mechanism of 7,4'-dihydroxyflavone in combination with vitamin D3 against asthma.

Ethnopharmacological Relevance: 7,4'-dihydroxyflavone (74DHF), extracted from Gancao (Rhizoma Glycyrrhizae), has demonstrated to mediate the asthma pathology, while Vitamin D3 (VD3) plays a role in asthma treatment due to its immunomodulatory effects. However, the potential molecular or systems mechanism of 74DHF in combination with VD3 against asthma has not yet been elucidated.

Aim Of The Study: The current study not only deepens our understanding of the complex synergistic mechanism of 74DHF andVD3 against asthma but also proposes a promising strategy to promote the development of combination therapy.

Materials And Methods: This study employed a systems pharmacology-based approach integrating target fishing, data integration, bioinformatics analysis, network analysis, Gene Ontology (GO) enrichment analysis, pathway analysis, and in vitro experiment validation to elucidate the pharmacological mechanisms of the combination of 74DHF and VD3 for asthma treatment.

Results: Our investigation revealed 47 overlapping targets, 20 core targets, 10 optimal common GO processes, and 10 key pathways closely associated with asthma in the combination of 74DHF and VD3. The combined treatment of 74DHF and VD3 inhibited the inflammatory response (TNF-α and IL-6) induced by LPS in macrophages and epithelial to mesenchymal transition (EMT) related genes expression (CDH1 and ACTA2) in bronchial epithelial cells under the stimulation of TGF-β1.

Conclusion: The present study deciphered the molecular mechanism of combined therapeutic effect of 74DHF and VD3 on asthma on systemic and cellular level.