Herb-symptom analysis of Erchen decoction combined with Xiebai powder formula and its mechanism in the treatment of chronic obstructive pulmonary disease

Abstract

Background: In recent years, the incidence and mortality rates of chronic obstructive pulmonary disease (COPD) have increased significantly. Erchen Decoction combined with Xiebai Powder (ECXB) formula is mainly used to treat lung diseases in traditional Chinese medicine (TCM). However, the active ingredients of ECXB formula, COPD treatment-related molecular targets, and the mechanisms are still unclear. To reveal its underlying action of mechanism, network pharmacology, molecular docking, and molecular dynamic (MD) simulation approaches were used to predict the active ingredients and potential targets of ECXB formula in treating COPD. As a result, Herb-Symptom analysis showed that the symptoms treated by both TCM and modern medicine of ECXB formula were similar to the symptoms of COPD. Network pharmacology identified 170 active ingredients with 137 targets, and 7,002 COPD targets was obtained. 120 targets were obtained by intersection mapping, among which the core targets include MAPK8, ESR1, TP53, MAPK3, JUN, RELA, MAPK1, and AKT1. Functional enrichment analysis suggested that ECXB formula might exert its treat COPD pharmacological effects in multiple biological processes, such as cell proliferation, apoptosis, inflammatory response, and synaptic connections, and ECXB formula treated COPD of the KEGG potential pathways might be associated with the TNF signaling pathway, cAMP signaling pathway, and VEGF signaling pathway. Molecular docking showed that ECXB formula treatment COPD core active ingredients can bind well to core targets. MD simulations showed that the RELA-beta-sitosterol complex and ESR1-stigmasterol complex exhibited higher conformational stability and lower interaction energy, further confirming the role of ECXB formula in the treatment of COPD through these core components and core targets. Our study analyzed the medication rule of ECXB formula in the treatment of COPD from a new perspective and found that the symptoms treated by both TCM and modern medicine of ECXB formula were similar to the symptoms of COPD. ECXB formula could treat COPD through multi-component, multi-target, and multi-pathway synergistic effects, providing a scientific basis for further study on the mechanism of ECXB formula treatment of COPD. It also provides new ideas for drug development.

Keywords: Erchen decoction; Xiebai powder; chronic obstructive pulmonary disease; herb-symptom analysis; synergistic mechanism; traditional Chinese medicine.

FIGURE 1

The flowchart of this study is based on Herb-Symptom analysis, network pharmacology, molecular docking, and molecular dynamics simulation for deciphering the potential mechanisms of ECXB formula treatment COPD.

FIGURE 2

“Herb-TCM Symptom” network diagram. The pink node represents herbs, while green nodes show the TCM Symptoms.

FIGURE 3

“Herb-modern medicine Symptom” network diagram. The orange node represents herbs, while the blue nodes show modern medicine Symptoms.

FIGURE 4

Venn diagram of ECXB formula combined with COPD. The Venn map showed that 120 targets were shared between ECXB formula and COPD.

FIGURE 5

“Drug-ingredient-target” network diagram of ECXB formula in the treatment of COPD. The node size and node label size are determined by the node degree value. The higher the degree value, the larger will be the node and label.

FIGURE 6

Protein interaction network diagram. 120-node and 424-edge PPI network of potential targets of the ECXB formula working on COPD was acquired at the String database.

FIGURE 7

Core protein interaction network. (A) Interactive PPI network of ECXB formula-related targets and COPD-related targets. (B) PPI network of significant proteins extracted from (A). (C) PPI network of candidate COPD targets for ECXB formula treatment extracted from (B).

FIGURE 8

Functional enrichment analysis of the top 10 in GO. The Y-axis shows the enriched GO items of target genes. The X-axis shows the gene counts for the items. The color indicates the q value.

FIGURE 9

The first 20 KEGG pathways. The Y-axis shows the enriched KEGG pathways for target genes. The X-axis shows the gene counts for the items. The color indicates the p-value.

FIGURE 10

Target-signal pathway network diagram. The orange boxes indicate the signal pathways. The blue boxes indicate the gene names.

FIGURE 11

The TNF-α signaling pathway of potential target genes of ECXB formula in COPD. Arrows indicate upstream and downstream relationships between genes. The red blocks are ECXB formula target genes in the network.

FIGURE 12

Diagram of molecular docking results. Proteins are shown to interact with molecules. The docking scores are shown in the middle. The binding amino acidic sites and other details are shown on the right.

FIGURE 13

The MD simulation results of two complexes. (A) The RMSD analysis for the RELA-beta-sitosterol complex. (B) The RMSD analysis for the ESR1-stigmasterol complex. (C) The RMSF analysis for the RELA-beta-sitosterol complex. (D) The RMSF analysis for the ESR1-stigmasterol complex.