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

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

Effect of BJF on IL-1β, IL-6 TNF-α, and sTNFR2 expression in COPD rat lung tissue. IL-1β, IL-6, TNF-α, and sTNFR2 in lung tissues were detected with immunohistochemistry (magnification, ×100) on week 32 (a). Quantitative analysis for IL-6, IL-1β, TNF-α, and sTNFR2 expression was performed (b). Results were given as means ± SEM and ∗∗p < 0.01 versus model.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5382313&req=5

fig3: Effect of BJF on IL-1β, IL-6 TNF-α, and sTNFR2 expression in COPD rat lung tissue. IL-1β, IL-6, TNF-α, and sTNFR2 in lung tissues were detected with immunohistochemistry (magnification, ×100) on week 32 (a). Quantitative analysis for IL-6, IL-1β, TNF-α, and sTNFR2 expression was performed (b). Results were given as means ± SEM and ∗∗p < 0.01 versus model.

Mentions: The inflammatory cytokines are the central mediators in many immune-mediated pulmonary diseases, such as COPD [17–19]. Thus, we evaluated the long-term effect of BJF on the expression levels of inflammatory cytokines in the lung and serum. Compared with model rat, BJF and aminophylline significantly suppressed the levels of IL-1β, IL-6, TNF-α, and sTNFR2 in lung tissues on week 32 (Figure 3). There are many evidences suggesting the excessive pulmonary inflammation is believed to result in “spill-over” into the systemic inflammation [18]. We then analyzed the levels of IL-1β, IL-6, TNF-α, and sTNFR2 in serum on week 32. We observed BJF treatment significantly decreased these inflammatory cytokines levels in serum (Figure 4).


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 IL-1β, IL-6 TNF-α, and sTNFR2 expression in COPD rat lung tissue. IL-1β, IL-6, TNF-α, and sTNFR2 in lung tissues were detected with immunohistochemistry (magnification, ×100) on week 32 (a). Quantitative analysis for IL-6, IL-1β, TNF-α, and sTNFR2 expression was performed (b). Results were given as means ± SEM and ∗∗p < 0.01 versus model.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382313&req=5

fig3: Effect of BJF on IL-1β, IL-6 TNF-α, and sTNFR2 expression in COPD rat lung tissue. IL-1β, IL-6, TNF-α, and sTNFR2 in lung tissues were detected with immunohistochemistry (magnification, ×100) on week 32 (a). Quantitative analysis for IL-6, IL-1β, TNF-α, and sTNFR2 expression was performed (b). Results were given as means ± SEM and ∗∗p < 0.01 versus model.
Mentions: The inflammatory cytokines are the central mediators in many immune-mediated pulmonary diseases, such as COPD [17–19]. Thus, we evaluated the long-term effect of BJF on the expression levels of inflammatory cytokines in the lung and serum. Compared with model rat, BJF and aminophylline significantly suppressed the levels of IL-1β, IL-6, TNF-α, and sTNFR2 in lung tissues on week 32 (Figure 3). There are many evidences suggesting the excessive pulmonary inflammation is believed to result in “spill-over” into the systemic inflammation [18]. We then analyzed the levels of IL-1β, IL-6, TNF-α, and sTNFR2 in serum on week 32. We observed BJF treatment significantly decreased these inflammatory cytokines levels in serum (Figure 4).

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