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Integrating Transcriptomics, Proteomics, and Metabolomics Profiling with System Pharmacology for the Delineation of Long-Term Therapeutic Mechanisms of Bufei Jianpi Formula in Treating COPD

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ABSTRACT

In previous work, we identified 145 active compounds from Bufei Jianpi formula (BJF) by system pharmacology and found that BJF showed short-term effect on chronic obstructive pulmonary disease (COPD) rats. Here, we applied the transcriptomic, proteomic, and metabolomics approaches to illustrate the long-term anti-COPD action and its system mechanism of BJF. BJF has obvious anti-COPD effect through decreasing inflammatory cytokines level, preventing protease-antiprotease imbalance and collagen deposition on week 32 by continuous oral administration to rats from weeks 9 to 20. Subsequently, applying the transcriptomic, proteomic, and metabolomics techniques, we detected a number of regulated genes, proteins, and metabolites, mainly related to antioxidant activity, focal adhesion, or lipid metabolism, in lung tissues of COPD and BJF-treated rats. Afterwards, we integrated system pharmacology target, transcript, protein, and metabolite data sets and found that many genes, proteins, and metabolites in rats BJF-treated group and the target proteins of BJF were mainly attributed to lipid metabolism, inflammatory response, oxidative stress, and focal adhesion. Taken together, BJF displays long-term anti-COPD effect probably by system regulation of the lipid metabolism, inflammatory response pathways oxidative stress, and focal adhesion.

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Correlation analysis of genes, proteins, and metabolites regulated in COPD rat and BJF-treated rat lung tissues. Metabolites-gene network analysis of COPD model (a) and BJF-treated group (b). Metabolites-protein network analysis of COPD model (c) and BJF-treated group (d). Networks of the metabolites, genes, and proteins were visualized by Metscape (hexagon node: compounds, round node: metabolic enzymes, and edge: reactions. Red: inputted genes and proteins; blue: inputted compounds).
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fig10: Correlation analysis of genes, proteins, and metabolites regulated in COPD rat and BJF-treated rat lung tissues. Metabolites-gene network analysis of COPD model (a) and BJF-treated group (b). Metabolites-protein network analysis of COPD model (c) and BJF-treated group (d). Networks of the metabolites, genes, and proteins were visualized by Metscape (hexagon node: compounds, round node: metabolic enzymes, and edge: reactions. Red: inputted genes and proteins; blue: inputted compounds).

Mentions: We firstly built the gene-metabolite networks based on the transcriptomics and metabolomics data of model and BJF-treated rats. We observed these genes and metabolites were primarily involved in lipid, purine, or energy metabolism (Figures 10(a) and 10(b)). Similarly, we constructed metabolite-protein networks, which contained three main parts: lipid metabolism, purine metabolism, or glutathione metabolism (Figures 10(c) and 10(d)). These results suggested that lipid metabolism played an important role in COPD progression and long-term anti-COPD effect of BJF.


Integrating Transcriptomics, Proteomics, and Metabolomics Profiling with System Pharmacology for the Delineation of Long-Term Therapeutic Mechanisms of Bufei Jianpi Formula in Treating COPD
Correlation analysis of genes, proteins, and metabolites regulated in COPD rat and BJF-treated rat lung tissues. Metabolites-gene network analysis of COPD model (a) and BJF-treated group (b). Metabolites-protein network analysis of COPD model (c) and BJF-treated group (d). Networks of the metabolites, genes, and proteins were visualized by Metscape (hexagon node: compounds, round node: metabolic enzymes, and edge: reactions. Red: inputted genes and proteins; blue: inputted compounds).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5382313&req=5

fig10: Correlation analysis of genes, proteins, and metabolites regulated in COPD rat and BJF-treated rat lung tissues. Metabolites-gene network analysis of COPD model (a) and BJF-treated group (b). Metabolites-protein network analysis of COPD model (c) and BJF-treated group (d). Networks of the metabolites, genes, and proteins were visualized by Metscape (hexagon node: compounds, round node: metabolic enzymes, and edge: reactions. Red: inputted genes and proteins; blue: inputted compounds).
Mentions: We firstly built the gene-metabolite networks based on the transcriptomics and metabolomics data of model and BJF-treated rats. We observed these genes and metabolites were primarily involved in lipid, purine, or energy metabolism (Figures 10(a) and 10(b)). Similarly, we constructed metabolite-protein networks, which contained three main parts: lipid metabolism, purine metabolism, or glutathione metabolism (Figures 10(c) and 10(d)). These results suggested that lipid metabolism played an important role in COPD progression and long-term anti-COPD effect of BJF.

View Article: PubMed Central - PubMed

ABSTRACT

In previous work, we identified 145 active compounds from Bufei Jianpi formula (BJF) by system pharmacology and found that BJF showed short-term effect on chronic obstructive pulmonary disease (COPD) rats. Here, we applied the transcriptomic, proteomic, and metabolomics approaches to illustrate the long-term anti-COPD action and its system mechanism of BJF. BJF has obvious anti-COPD effect through decreasing inflammatory cytokines level, preventing protease-antiprotease imbalance and collagen deposition on week 32 by continuous oral administration to rats from weeks 9 to 20. Subsequently, applying the transcriptomic, proteomic, and metabolomics techniques, we detected a number of regulated genes, proteins, and metabolites, mainly related to antioxidant activity, focal adhesion, or lipid metabolism, in lung tissues of COPD and BJF-treated rats. Afterwards, we integrated system pharmacology target, transcript, protein, and metabolite data sets and found that many genes, proteins, and metabolites in rats BJF-treated group and the target proteins of BJF were mainly attributed to lipid metabolism, inflammatory response, oxidative stress, and focal adhesion. Taken together, BJF displays long-term anti-COPD effect probably by system regulation of the lipid metabolism, inflammatory response pathways oxidative stress, and focal adhesion.

No MeSH data available.


Related in: MedlinePlus