Evaluation of the Efficacy of Jiangqi Dingchuan Pill Based on Network Pharmacology Analysis and Cigarette Smoke and Lipopolysaccharide Induced Chronic Obstructive Pulmonary Disease Rat Model

Abstract

Background: Jiangqi Dingchuan Pill (JDP) is a patent Chinese medicine in the treatment of asthma. JDP consists of six herbal drugs, namely, Ephedrae Herba, Mori Cortex, Citri Reticulatae Pericarpium, Perillae Fructus, Descurainiae Semen, Sinapis Semen.

Objective: To employ the tools of network pharmacology and in vivo experiments, exploring the possible mechanism of JDP in treating chronic obstructive pulmonary disease (COPD).

Materials and methods: Chemical constituents of JDP, collection of targets of COPD, target prediction were conducted, and then network pharmacological analysis was performed based on protein-protein interaction (PPI). The cigarette smoke and lipopolysaccharide-induced COPD model was applied to assess the effects of JDP. Rats were randomly divided into five groups (n = 8), ie, a sham group, a COPD-control group, two COPD groups treated with different doses of JDP (1.26 and 2.52 g/kg/d, respectively), and one COPD group treated with aminophylline (54 mg/kg/d). Pulmonary functions were assessed. The inflammatory cytokines in bronchial alveolar lavage fluid (BALF) were quantified using enzyme-linked immunosorbent assay (ELISA). The expression of matrix metalloprotein-9 (MMP-9) was quantified using Western blot.

Results: A total of 108 genes were found to be the main target genes regulated by JDP in the treatment of COPD, according to PPI analysis. Compared with the COPD-control group, rats in the JDP group exhibited amelioration in lung function, including 20 ms forced expiratory volume/forced vital capacity, maximal mid-expiratory flow curve, and airway resistance (all p < 0.05). A reduction of IL-1β and TNF-α expressions in BALF was also observed (both p < 0.05). Compared with the COPD-control group, the expression of MMP-9 in lung tissue was down-regulated in the JDP group (p < 0.05).

Conclusion: This study explored the effects and its mechanisms of JDP in COPD treatment. JDP exhibited therapeutic potential as a COPD intervention drug.

Keywords: Jiangqi Dingchuan Pill; Traditional Chinese Medicine; chronic obstructive pulmonary disease; network pharmacology.

Graphical abstract

Figure 1

PPI network and network intersection. (A) PPI network of JDP with 635 nodes and 4984 edges. (B) PPI network of COPD with 290 nodes and 1100 edges. (C) Venn diagram of high confident interaction of PPI network between JDP and COPD. (D) Visualization of central PPI network of JDP treating COPD. In (A) and (B), the yellow nodes denoted the intersected PPI network nodes between JDP and COPD, while the blue are those not intersected.

Figure 2

GO functional annotation and KEGG analysis of central network genes of JDP treating COPD. Biological process (A), molecular function (B), cellar components (C), and KEGG pathways (D) were sorted according to − log FDR (all p < 0.01).

Figure 3

Component-target-pathway network of JDP in the treatment of COPD. In the diagram, nodes are represented by a gradient of red to green coloration. Nodes in red are considered as important (with higher degree value), and the green nodes are considered as less important (with lower degree value). The inner grid denotes the major chemical components of the compound formula. The ellipses within the circles represent the main target genes regulated by the JDP. The outer rectangles at both sides denote the key biological processes regulated by the JDP.

Figure 4

Experimental flow chart and animal weight changes. (A) Experimental flow chart. (B) animal weight changes. n=8. *p < 0.05, versus sham group. Data are presented as mean±standard deviation. One-way ANOVA was employed for comparing means among multiple samples, and post hoc pairwise comparisons were conducted using the LSD method.

Figure 5

Effects of JDP on BALF cytokines, n=8. (A) IL-1β expression in BALF. (B) TNF-α expression in BALF. **p < 0.01, *p < 0.05, versus sham group. ^##p < 0.01, versus COPD-control group. Data are presented as mean±standard deviation. One-way ANOVA was employed for comparing means among multiple samples, and post hoc pairwise comparisons were conducted using the LSD method.

Figure 6

Effects of JDP on MMP9 protein expression in the lung. (A) Representative Western blotting for MMP9. (B) Quantitative analysis of Western blotting of MMP9. In each group, n=3. ^##p < 0.01, versus COPD-control group. Data are presented as mean±standard deviation. One-way ANOVA was employed for comparing means among multiple samples, and post hoc pairwise comparisons were conducted using the LSD method.