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Bioinformatics and Network Pharmacology Identify the Therapeutic Role of Guominkang in Allergic Asthma by Inhibiting
Honglei Zhang1,2, Haiyun Zhang1,2,3, Lei Wang4
1National Institute of TCM Body Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China.
Background:
As a classical regulating formula, Guominkang (GMK) has been extensively employed in clinical practice to treat the allergic asthma (AA) and alleviate allergy symptoms, however, the underlying mechanism remains elusive. The aim of this study was to explored the mechanism of action through which GMK combats AA.
Methods:
Potential target genes for the compounds were identified from the database and subjected to functional enrichment analysis. Subsequently, a protein-protein interaction (PPI) network was constructed in order to screen the core target and confirmed by molecular docking. An asthma model was further developed in mice and airway hyperresponsiveness and lung pathological changes were observed following drug administration. The expression of PI3K and AKT proteins in lung tissues was then detected by Western blotting. Subsequently, the GSE104468 data were normalised and visualised using the R language, compared to the PI3K-Akt pathway gene set to identify overlapping genes, constructed a PPI network and analysed correlations between genes.
Results:
267 compounds and 475 disease-relevant GMK targets have been obtained, primarily in the areas of chemokine binding, drug binding, and PI3K-Akt pathway modulation. Molecular docking simulations revealed that predicted targets (PI3K, TNF, IL6, AKT1, SRC, TP53, and STAT3) could be closely bonded with component of GMK. According to in vivo experiments, GMK could reduce mucus obstruction and airway inflammation (P < 0.05), decrease airway hyperresponsiveness (P < 0.05), and inhibited the PI3K-Akt pathway (P < 0.05). After normalising the genes in the dataset between AA and healthy individuals, GO showed that 388 DEGs were associated with PI3K/AKT signaling pathway. The PPI network showed that the overlapping gene were located in the centre of asthma-associated network and that exhibited a correlation with the PI3K-Akt signaling pathway.
Conclusion:
Based on our findings, GMK potentially acts via the PI3K/Akt pathway and alleviates allergic symptoms in AA.
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