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International Journal of Chronic Obstructive Pulmonary Disease Volume 11, 2016 - Issue
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Original Research

Combining systems pharmacology, transcriptomics, proteomics, and metabolomics to dissect the therapeutic mechanism of Chinese herbal Bufei Jianpi formula for application to COPD

Peng Zhao1 Key Laboratory of Chinese Internal Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, People’s Republic of China;2 Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, People’s Republic of China
,
Liping Yang1 Key Laboratory of Chinese Internal Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, People’s Republic of China;2 Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, People’s Republic of China
,
Jiansheng Li1 Key Laboratory of Chinese Internal Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, People’s Republic of China;2 Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, People’s Republic of ChinaCorrespondence[email protected]
,
Ya Li1 Key Laboratory of Chinese Internal Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, People’s Republic of China;2 Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, People’s Republic of China
,
Yange Tian1 Key Laboratory of Chinese Internal Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, People’s Republic of China;2 Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, People’s Republic of China
&
Suyun Li2 Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, People’s Republic of China;3 Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, People’s Republic of China
Pages 553-566 | Published online: 15 Mar 2016

Figures & data

Figure 1 Molecular functions of regulated genes in lung tissues of rats with COPD and BJF-treated rats.

Notes: BiNGO mapped the predominant functional themes of the tested gene set on the GO hierarchy and produced an intuitive and a customizable visual representation of the results. The area of a node was proportional to the number of genes in the test set annotated to the corresponding GO category. (A) Representative molecular function of regulated genes in lung tissues of rats with COPD. (B) Representative molecular function of regulated genes in lung tissues of BJF-treated rats.
Abbreviations: BJF, Bufei Jianpi formula; GO, gene ontology; FAD, flavin adenine dinucleotide.
Figure 1 Molecular functions of regulated genes in lung tissues of rats with COPD and BJF-treated rats.

Table 1 Analyzed pathways of transcriptomics data regulated in lung tissues of rats with COPD

Table 2 Analyzed pathways of transcriptomics data regulated in lung tissues of Bufei-Jianpi-formula-treated rats

Figure 2 Molecular functions of regulated proteins in lung tissues of COPD rats and BJF-treated rats.

Notes: BiNGO mapped the predominant functional themes of the 42 overlapping proteins between COPD rats and BJF-treated rats and produced an intuitive and a customizable visual representation of the results (A). The molecular functions of 192 regulated proteins in COPD rats (B), and 191 regulated proteins in BJF-treated rats (C) were analyzed by ClueGO: functionally grouped network with terms as nodes linked, and functionally related groups partially overlap; the node size represents the term enrichment significance.
Abbreviation: BJF, Bufei Jianpi formula.
Figure 2 Molecular functions of regulated proteins in lung tissues of COPD rats and BJF-treated rats.
Figure 2 Molecular functions of regulated proteins in lung tissues of COPD rats and BJF-treated rats.

Table 3 Analyzed pathways of proteomics data regulated in lung tissues of rats with COPD

Table 4 Analyzed pathways of proteomics data regulated in lung tissues of Bufei-Jianpi-formula-treated rats

Figure 3 Pathway analysis of the metabolites regulated in lung tissues of COPD rats and BJF-treated rats.

Notes: Global metabolic disorders of the most relevant pathways were revealed using the MetaboAnalyst. A Google-map style interactive visualization system was implemented to facilitate data exploration and generate pathway views. (A) Representative pathway analysis of the metabolites in lung tissues of COPD rats. (B) Representative pathway analysis of the metabolites in lung tissues of BJF-treated rats.
Abbreviation: BJF, Bufei Jianpi formula.
Figure 3 Pathway analysis of the metabolites regulated in lung tissues of COPD rats and BJF-treated rats.

Figure 4 Correlation networks of the metabolites, genes, and proteins regulated in lung tissues of COPD rats and BJF-treated rats.

Notes: The compound reaction network with compounds (the pink and red hexagons) and metabolic enzymes (the gray and blue rounds) as nodes and reactions as edges, was constructed using Metscape. Inputted compounds are shown in red, inputted genes and proteins are shown in blue. Existing compounds that populate the Metscape system were shown in pink. Existing genes and proteins were shown in gray. (A) Representative metabolites–gene network of COPD model group. (B) Representative metabolite–gene network of the BJF-treated group. (C) Representative metabolites–protein network of the COPD model group. (D) Representative metabolite–protein network of the BJF-treated group.
Abbreviation: BJF, Bufei Jianpi formula.
Figure 4 Correlation networks of the metabolites, genes, and proteins regulated in lung tissues of COPD rats and BJF-treated rats.

Figure 5 Molecular functions of the overlapping proteins.

Notes: BiNGO mapped the predominant functional themes of the tested protein set on the GO hierarchy and produced an intuitive and customizable visual representation of the results. The area of a node was proportional to the number of proteins in the test set annotated to the corresponding GO category. (A) Representative molecular function of overlapping proteins between the potential targets and transcript measurements in lung tissues of BJF-treated rats. (B) Representative molecular function of overlapping proteins between the potential targets and proteome measurements in lung tissues of BJF-treated rats.

Abbreviation: BJF, Bufei Jianpi formula.

Figure 5 Molecular functions of the overlapping proteins.Notes: BiNGO mapped the predominant functional themes of the tested protein set on the GO hierarchy and produced an intuitive and customizable visual representation of the results. The area of a node was proportional to the number of proteins in the test set annotated to the corresponding GO category. (A) Representative molecular function of overlapping proteins between the potential targets and transcript measurements in lung tissues of BJF-treated rats. (B) Representative molecular function of overlapping proteins between the potential targets and proteome measurements in lung tissues of BJF-treated rats.Abbreviation: BJF, Bufei Jianpi formula.

Figure 6 Correlation networks of the metabolites regulated in BJF-treated rats and target proteins.

Notes: The compound reaction network with compounds (the pink and red hexagons) and metabolic enzymes (the gray and blue rounds) as nodes and reactions as edges, was constructed using Metscape. Inputted compounds are shown in red, and inputted target proteins are shown in blue. Existing compounds that populate the Metscape system were shown in pink. Existing proteins were shown in gray.
Abbreviation: BJF, Bufei Jianpi formula.
Figure 6 Correlation networks of the metabolites regulated in BJF-treated rats and target proteins.

Figure 7 Comprehensive analysis of the potential targets of BJF, transcriptomics, proteomics, and metabolomics regulations in lung tissues of BJF-treated rats.

Notes: The potential targets, transcriptomics, proteomics, and metabolomics data are presented as rectangles with different colors. Red arrow stands for upregulated, blue arrow for downregulated, and gray rectangle for unregulated.
Abbreviation: BJF, Bufei Jianpi formula.
Figure 7 Comprehensive analysis of the potential targets of BJF, transcriptomics, proteomics, and metabolomics regulations in lung tissues of BJF-treated rats.

Table 5 Analyzed pathways of the potential target

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