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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.

No MeSH data available.


Related in: MedlinePlus

Effect of BJF on the pulmonary function. TV (a), PEF (b), and EF50 (c) were examined every four weeks from weeks 0 to 32. Results were given as means ± SEM and ∗p < 0.05 versus model.
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fig1: Effect of BJF on the pulmonary function. TV (a), PEF (b), and EF50 (c) were examined every four weeks from weeks 0 to 32. Results were given as means ± SEM and ∗p < 0.05 versus model.

Mentions: To investigate the long-term anti-COPD action of BJF, we administrated BJF to COPD rats during weeks 9 to 20 and tested the effect of BJF on the functional and morphological changes of lung tissues. In Figure 1, compared with the model group, BJF and aminophylline markedly elevated the TV, PEF, and EF50 in COPD rat at week 32. Meanwhile, lung injury scores, bronchiole wall thickness, small pulmonary vessels wall thickness, bronchiole stenosis, and alveolar diameter markedly elevated in the COPD rats and this elevation was significantly inhibited by BJF (Figures 2(a)–2(f)). Reduction of alveolar number in COPD rats was significantly suppressed by BJF (Figure 2(g)). These findings indicated that BJF showed long-term anti-COPD on COPD rats.


Integrating Transcriptomics, Proteomics, and Metabolomics Profiling with System Pharmacology for the Delineation of Long-Term Therapeutic Mechanisms of Bufei Jianpi Formula in Treating COPD
Effect of BJF on the pulmonary function. TV (a), PEF (b), and EF50 (c) were examined every four weeks from weeks 0 to 32. Results were given as means ± SEM and ∗p < 0.05 versus model.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5382313&req=5

fig1: Effect of BJF on the pulmonary function. TV (a), PEF (b), and EF50 (c) were examined every four weeks from weeks 0 to 32. Results were given as means ± SEM and ∗p < 0.05 versus model.
Mentions: To investigate the long-term anti-COPD action of BJF, we administrated BJF to COPD rats during weeks 9 to 20 and tested the effect of BJF on the functional and morphological changes of lung tissues. In Figure 1, compared with the model group, BJF and aminophylline markedly elevated the TV, PEF, and EF50 in COPD rat at week 32. Meanwhile, lung injury scores, bronchiole wall thickness, small pulmonary vessels wall thickness, bronchiole stenosis, and alveolar diameter markedly elevated in the COPD rats and this elevation was significantly inhibited by BJF (Figures 2(a)–2(f)). Reduction of alveolar number in COPD rats was significantly suppressed by BJF (Figure 2(g)). These findings indicated that BJF showed long-term anti-COPD on COPD rats.

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