Investigating the mechanism of action of Yanghe Pingchuan Granule in the treatment of bronchial asthma based on bioinformatics and experimental validation

Chunxia Gong; Lingyu Pan; Yeke Jiang; Yehong Sun; Yanquan Han; Dianlei Wang; Yongzhong Wang

doi:10.1016/j.heliyon.2023.e21936

Investigating the mechanism of action of Yanghe Pingchuan Granule in the treatment of bronchial asthma based on bioinformatics and experimental validation

Heliyon. 2023 Nov 2;9(11):e21936. doi: 10.1016/j.heliyon.2023.e21936. eCollection 2023 Nov.

Authors

Chunxia Gong^{1

2}, Lingyu Pan¹, Yeke Jiang^{1

2}, Yehong Sun^{1

2}, Yanquan Han¹, Dianlei Wang², Yongzhong Wang¹

Affiliations

¹ The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, 230031, China.
² College of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, 230038, China.

Abstract

Background: Yanghe Pingchuan Granule (YPG) is a patented Chinese medicine developed independently by the Anhui Provincial Hospital of Traditional Chinese Medicine. For many years, it has been used for the treatment of asthma with remarkable clinical effects. However, the composition of YPG is complex, and its potential active ingredients and mechanism of action for the treatment of asthma are unknown.

Materials and methods: In this study, we investigated the potential mechanism of action of YPG in the treatment of asthma through a combination of bioinformatics and in vivo experimental validation. We searched for active compounds in YPG and asthma targets from multiple databases and obtained common targets. Subsequently, a protein-protein interaction (PPI) network for compound disease was constructed using the protein interaction database for Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, hematoxylin and eosin (H&E) staining, Masson staining, enzyme-linked immunosorbent assay (ELISA) analysis, immunofluorescence (IF) experiments, and Western blot (WB) experiments were performed to verify the possible mechanism of action of YPG for asthma treatment.

Results: We obtained 72 active ingredients and 318 drug target genes that overlap with asthma. Serine/threonine-protein kinase (AKT1), tumor protein p53 (TP53), tumor necrosis factor (TNF), interleukin (IL)-6, IL-1β, vascular endothelial growth factor-A (VEGFA), prostaglandin-endoperoxide synthase 2 (PTGS2), caspase-3 (CASP3), mitogen-activated protein kinase 3 (MAPK3) and epidermal growth factor receptor (EGFR) were the most relevant genes in the PPI network. KEGG analysis showed a high number of genes enriched for the nuclear factor kappa-B (NF-κB) signaling pathway. Animal experiments confirmed that YPG reduced inflammatory cell infiltration and down-regulated the expression of ovalbumin-induced inflammatory factors. Furthermore, YPG treatment decreased the protein expression of NFĸB1, nuclear factor kappa B kinase subunit beta (IKBKB), vascular endothelial growth factor (VEGF), and vascular endothelial growth factor receptor 2 (VEGFR2) in lung tissue.

Conclusion: YPG has a positive effect on asthma by interfering with multiple targets. Furthermore, YPG may significantly inhibit the follicle-induced inflammatory response through the NF-ĸB signaling pathway.

Keywords: Asthma; Bioinformatics; Experimental validation; NF-кB signaling pathway; Yanghe Pingchuan granule.