Animal experiment results
As shown in Figure 2, according to the pathological HE staining results of lung tissue, the alveolar structure of normal group was intact, the wall was thin, no inflammatory infiltration was observed, and the bronchioles were intact and clear; compared with the normal group, the lung tissue structure in the pneumonia group was damaged; the alveolar septum was different in size; the alveolar wall was thickened and fractured; a large number of neutrophil infiltration and erythrocyte extravasation were seen in the interstitial lung; and vascular endothelial cell proliferation was observed. Compared the two treatment groups with the pneumonia group, the lung tissue and alveoli structure in rats became clear, and the interstitial hyperplasia was alleviated with a small amount of inflammatory infiltration.
Test results of honeysuckle and dexamethasone
According to the qualification conditions, 31 honeysuckle components were obtained, and a total of 3 compounds were identified by comparison with the standard, as shown in Figure 3, Table 1 and supplementary data Figure 1.
Network diagram and analysis of “drug-ingredient-action target”
After removing the repeated targets, 545 honeysuckle aqueous extracts and 34 dexamethasone targets were finally obtained. The drug component and its corresponding target were introduced into the Cytoscape 3.6 software, and the “component-target network map” was drawn (see Figure 4, Figure 5). The honeysuckle network diagram contains 645 nodes and 631 edges; the dexamethasone network diagram contains 35 nodes and 34 edges.
Predictive target of honeysuckle/dexamethasone against pneumonia
A total of 30083 related targets for pneumonia were obtained. After matching the drug component corresponding target, 366 targets common to honeysuckle and 30 targets common to dexamethasone were obtained, that is, the predictive target of honeysuckle/dexamethasone against pneumonia. Among them, there are 8 target proteins common to honeysuckle and dexamethasone against pneumonia, respectively are: CD38, ENPP1, ESR1, IL1B, NR3C2, PGR, PLA2G4A, RPS6KA3. The relationship between the targets is shown in Figure 6, and the common targets are shown in supplementary data table 1.
Potential target interaction network and analysis
As shown in Figure 7, the left side is the network diagram of predicted target of honeysuckle in the treatment of pneumonia; the right side is the network diagram of the target of dexamethasone in the treatment of pneumonia. The honeysuckle network diagram contains 365 circular nodes, representing all the predicted targets; 2749 edges, representing the correlation between the targets; the dexamethasone network diagram contains 29 circular nodes and 67 edges; the darker the color of the nodes, it means that the bigger the value of its Degree is. According to the value of Degree, 18 of the top 5% of honeysuckle were GAPDH (101), TNF (71), FOS (66), VEGFA (65), BDNF (64), CASP3 (59), CXCL8 ( 56), PTEN (55), MTOR (52), F2 (51), CXCL12 (51), PTGS2 (49), EDN1 (48), TH (47), ESR1 (47), IL1B (45), GPT ( 44), NPY (43); one of the first 5% of dexamethasone targets is MYC (12). In the brackets is Cytoscape Degree. These targets have the greatest correlation with the treatment of pneumonia, which is the core target.
GO and KEGG pathway enrichment results and analysis
The results of GO enrichment analysis of honeysuckle aqueous extracts showed that the high enrichment of biological process (BP) analysis are response to organic substance, response to endogenous stimulus, response to hypoxia, response to oxygen levels, positive regulation of multicellular Organismal process; the high enrichment of cell component (CC) analysis are cell fraction, Cytosol, insoluble fraction, axon, neuron projection, etc.; the high enrichment of molecular function (MF) analysis are pyridoxal phosphate binding, vitamin B6 binding, vitamin binding, cofactor binding, transferase activity, transferring nitrogenous groups and so on. Through KEGG pathway enrichment analysis, Glycine, serine and threonine metabolism, Nitrogen metabolism, Neuroactive ligand-receptor interaction, Calcium signaling pathway, Phenylalanine metabolism pathways, etc. are closely related to the treatment of pneumonia with honeysuckle.
Compared with honeysuckle, the results of GO enrichment analysis of dexamethasone showed that the high enrichment of BP analysis are regulation of apoptosis, regulation of programmed cell death, regulation of cell death, regulation of cell proliferation, response to organic substance, etc.; the high enrichment of CC analysis are cell surface, secretory granule, etc.; the high enrichment of MF analysis are steroid hormone receptor activity, ligand-dependent nuclear receptor activity, sequence-specific DNA binding, steroid binding, transcription factor activity, and so on. The KEGG pathway enrichment analysis speculated that MAPK signaling pathway is closely related to dexamethasone in the treatment of pneumonia.
Construction and analysis of the “component-target-path” network
As shown in Figure 9, the mechanisms of the dexamethasone core was predicted to be the dexamethasone-MYC-MAPK signaling pathway. After removing the signaling pathways of Alzheimer’s, Parkinson’s and prostate cancer’s three specific diseases, the mechanisms prediction network of honeysuckle intervention pneumonia, including 4 small molecule compounds, 5 target proteins and 6 signaling pathways, constitutes 12 pathways, see Table 2, of which the most likely mechanism is the Inositol-PTEN-Phosphatidylinositol signaling system.
Molecular docking results and analysis
Based on the above results, dexamethasone-MYC and Inositol-PTEN were molecularly docked respectively. The results are shown in supplementary data table 2. The binding energy of DXMS-MYC (6g6j) was -8.1 kcal/mol, and the binding energy of Inositol-PTEN (5bzz) was -5.8 kcal/mol. As can be seen from Figure 10, two molecules were tightly bound to the groove portion of the target protein receptor. Among them, DXMS had hydrogen-bond interaction with two amino acid molecules, and Inositol had hydrogen-bond interacts with 9 amino acid molecules.