Advanced search
Publication Cover
International Journal of Chronic Obstructive Pulmonary Disease Volume 10, 2015 - Issue
Submit an article Journal homepage
115
Views
10
CrossRef citations to date
0
Altmetric
Original Research

Systems pharmacology-based approach for dissecting the active ingredients and potential targets of the Chinese herbal Bufei Jianpi formula for the treatment of COPD

Peng Zhao1 Key Laboratory of Chinese Internal Medicine, Henan University of Traditional Chinese Medicine, People’s Republic of China;2 Key Laboratory of Chinese Internal Medicine, Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, Zhengzhou, People’s Republic of China
,
Jiansheng Li1 Key Laboratory of Chinese Internal Medicine, Henan University of Traditional Chinese Medicine, People’s Republic of China;2 Key Laboratory of Chinese Internal Medicine, Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, Zhengzhou, People’s Republic of ChinaCorrespondence[email protected]
,
Ya Li1 Key Laboratory of Chinese Internal Medicine, Henan University of Traditional Chinese Medicine, People’s Republic of China;2 Key Laboratory of Chinese Internal Medicine, Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, Zhengzhou, People’s Republic of China
,
Yange Tian1 Key Laboratory of Chinese Internal Medicine, Henan University of Traditional Chinese Medicine, People’s Republic of China;2 Key Laboratory of Chinese Internal Medicine, Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, Zhengzhou, People’s Republic of China
,
Yonghua Wang2 Key Laboratory of Chinese Internal Medicine, Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, Zhengzhou, People’s Republic of China;3 Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, People’s Republic of China
&
Chunli Zheng3 Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, People’s Republic of China
Pages 2633-2656 | Published online: 07 Dec 2015

Figures & data

Table 1 Chemical information of 165 candidate compounds and their network parameters

Figure 1 Compound–target network (C–T network).

Notes: The C–T network was built by linking the candidate compounds (rhombus, blue) of eleven herbs (square, orange) and all their candidate targets (ellipse, green). The C–T network consists of eleven herbs and 1,849 compound–target interactions connecting the 131 candidate compounds to 175 targets.
Abbreviations: T, target; M, molecular; AR, Astragali Radix; PR, Polygonati Rhizoma; CR, Codonopsis Radix; AMR, Atractylodis Macrocephalae Rhizoma; Po, Poria; FTB, Fritillariae Thunbergii Bulbus; MOC, Magnoliae Officinalis Cortex; CRP, Citri Reticulatae Pericarpium; ATR, Asteris Tatarici Radix; AJH, Ardisiae Japonicae Herba; EH, Epimedii Herba.
Figure 1 Compound–target network (C–T network).

Figure 2 ClueGO analysis of the predicted targets.

Notes: Functionally grouped network with terms as nodes linked and functionally-related groups partially overlap. The node size represents the term enrichment significance. The node pie charts represent the molecular function, immune system processes, and reactome analysis of each target corresponding to their networks in this target set. The label of only the significant term per group is shown. (A) Representative molecular function interactions among targets. (B) Representative immune system processes interactions among targets. (C) Representative reactome analysis interactions among predicted targets. *Represents enrichment significance.
Abbreviations: AP-1, activator protein-1; EGFR,epidermal growth factor receptor; GRB2, growth factor receptor-bound protein 2; MAPK, mitogen-activated protein kinase; NADPH, nicotinamide adenine dinucleotide phosphate.
Figure 2 ClueGO analysis of the predicted targets.
Figure 2 ClueGO analysis of the predicted targets.

Figure 3 Target–disease network (T–D network).

Notes: In the T–D network, candidate targets were connected with related diseases. Target proteins (133, ellipse, green) are connected to 348 diseases (rhombus, blue), which are classified into 16 groups (square, orange).
Abbreviations: D, disease; T, target.
Figure 3 Target–disease network (T–D network).

Figure 4 Effect of Bufei Jianpi formula (BJF) and aminophylline (APL) on pulmonary function of chronic obstructive pulmonary disease rats.

Notes: BJF (4.84 g/kg) and APL (2.3 mg/kg) were administered intragastrically once daily from weeks 9 to 20. Tidal volume (A), peak expiratory flow (B), and 50% tidal volume expiratory flow (C) were detected every 4th week from weeks 0 to 20. Values represent the mean ± standard error of mean. *P<0.05 vs model.

Figure 4 Effect of Bufei Jianpi formula (BJF) and aminophylline (APL) on pulmonary function of chronic obstructive pulmonary disease rats.Notes: BJF (4.84 g/kg) and APL (2.3 mg/kg) were administered intragastrically once daily from weeks 9 to 20. Tidal volume (A), peak expiratory flow (B), and 50% tidal volume expiratory flow (C) were detected every 4th week from weeks 0 to 20. Values represent the mean ± standard error of mean. *P<0.05 vs model.

Figure 5 Effects of Bufei Jianpi formula (BJF) and aminophylline (APL) on histological changes in hematoxylin and eosin (H&E)-stained lung sections of chronic obstructive pulmonary disease (COPD) rats.

Notes: On week 20, the lung tissues of COPD rats were collected. Histological changes were detected using H&E staining (original magnification ×100) (A). The lung injury scores of all groups were summarized (B). Bronchial wall thickness (C), bronchiole stenosis (D), small pulmonary vessels wall thickness (E), alveolar number (F), and alveolar diameter (G) were evaluated. Values represent the mean ± standard error of mean. *P<0.05, **P<0.01 vs model.
Figure 5 Effects of Bufei Jianpi formula (BJF) and aminophylline (APL) on histological changes in hematoxylin and eosin (H&E)-stained lung sections of chronic obstructive pulmonary disease (COPD) rats.

Figure 6 Effect of Bufei Jianpi formula (BJF) and aminophylline (APL) on changes in the myocardial ultrastructure and the right ventricular hypertrophy index (RVHI) of chronic obstructive pulmonary disease rats.

Notes: The muscular fibers (A) and mitochondria (B) of myocardial ultrastructure images were taken by transmission electron microscope (original magnification ×50,000). The sarcomere length (C), mitochondrial density (D), and RVHI (E) were evaluated. Values represent the mean ± standard error of mean. **P<0.01 vs model.

Figure 6 Effect of Bufei Jianpi formula (BJF) and aminophylline (APL) on changes in the myocardial ultrastructure and the right ventricular hypertrophy index (RVHI) of chronic obstructive pulmonary disease rats.Notes: The muscular fibers (A) and mitochondria (B) of myocardial ultrastructure images were taken by transmission electron microscope (original magnification ×50,000). The sarcomere length (C), mitochondrial density (D), and RVHI (E) were evaluated. Values represent the mean ± standard error of mean. **P<0.01 vs model.

Figure 7 Effect of BJF and APL on the expression of VEGF, bFGF, TGF-β, and ET-1 around the right ventricle obtained from chronic obstructive pulmonary disease rats.

Notes: Immunohistochemical staining of the right ventricle sections for VEGF, bFGF, TGF-β, and ET-1 (original magnification ×200) (A). Quantitative analysis for the expression of VEGF, bFGF, TGF-β, and ET-1 in the right ventricle (B). Values represent the mean ± standard error of mean. **P<0.01 vs model.
Abbreviations: VEGF, vascular endothelial growth factor; bFGF, basic fibroblast growth factor; TGF-β, transforming growth factor-β; ET-1, endothelin 1; BJF, Bufei Jianpi formula; APL, aminophylline; IOD, integral optical density.
Figure 7 Effect of BJF and APL on the expression of VEGF, bFGF, TGF-β, and ET-1 around the right ventricle obtained from chronic obstructive pulmonary disease rats.

Figure 8 Effect of Bufei Jianpi formula (BJF) and aminophylline (APL) on the expression of interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, and soluble TNF-α receptor 2 (sTNFR2) in the lung obtained from chronic obstructive pulmonary disease (COPD) rats.

Notes: Immunohistochemical staining of lung sections for IL-6, IL-10, TNF-α, and sTNFR2 (original magnification ×200) (A). Quantitative analysis for the expression of IL-6, IL-10, TNF-α, and sTNFR2 in the lung of COPD rats (B). Values represent the mean ± standard error of mean. **P<0.01 vs model.
Abbreviation: IOD, integral optical density.
Figure 8 Effect of Bufei Jianpi formula (BJF) and aminophylline (APL) on the expression of interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, and soluble TNF-α receptor 2 (sTNFR2) in the lung obtained from chronic obstructive pulmonary disease (COPD) rats.

Figure 9 Effect of Bufei Jianpi formula (BJF) and aminophylline (APL) on the expression of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of MMP (TIMP)-1 in the lung obtained from chronic obstructive pulmonary disease (COPD) rats.

Notes: Immunohistochemical and quantitative analysis for the expression of MMP-2, MMP-9, and TIMP-1 in the lung of COPD rats (original magnification ×200) (A). The messenger RNA (mRNA) levels of MMP-2, MMP-9, and TIMP-1 were analyzed with reverse transcriptase-polymerase chain reaction (B). Data are presented as mean ± standard error of mean. *P<0.05, **P<0.01 vs model.

Abbreviation: IOD, integral optical density.

Figure 9 Effect of Bufei Jianpi formula (BJF) and aminophylline (APL) on the expression of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of MMP (TIMP)-1 in the lung obtained from chronic obstructive pulmonary disease (COPD) rats.Notes: Immunohistochemical and quantitative analysis for the expression of MMP-2, MMP-9, and TIMP-1 in the lung of COPD rats (original magnification ×200) (A). The messenger RNA (mRNA) levels of MMP-2, MMP-9, and TIMP-1 were analyzed with reverse transcriptase-polymerase chain reaction (B). Data are presented as mean ± standard error of mean. *P<0.05, **P<0.01 vs model.Abbreviation: IOD, integral optical density.

Figure 10 Effect of Bufei Jianpi formula (BJF) and aminophylline (APL) on the expression of collagens I, III, and IV in the lung obtained from chronic obstructive pulmonary disease (COPD) rats.

Notes: Immunohistochemical analysis for the expression of collagens I, III, and IV in the lung of COPD rats (original magnification ×200) (A). Quantitative analysis for the expression of collagens I, III, and IV in the lungs of COPD rats (B). Data are presented as mean ± standard error of mean. *P<0.05, **P<0.01 vs model.
Abbreviation: IHS, immunohistochemical score.
Figure 10 Effect of Bufei Jianpi formula (BJF) and aminophylline (APL) on the expression of collagens I, III, and IV in the lung obtained from chronic obstructive pulmonary disease (COPD) rats.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.