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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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Overlapping proteins' molecular functions. BiNGO was applied to analyze the molecular functions of the overlapping proteins. (a) Molecular function analysis of overlapping proteins between the system pharmacology targets and transcript measurements in lung tissues BJF-treated rats. (b) Molecular function analysis of overlapping proteins between the potential targets and proteins regulated in BJF-treated rat lung tissues.
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fig11: Overlapping proteins' molecular functions. BiNGO was applied to analyze the molecular functions of the overlapping proteins. (a) Molecular function analysis of overlapping proteins between the system pharmacology targets and transcript measurements in lung tissues BJF-treated rats. (b) Molecular function analysis of overlapping proteins between the potential targets and proteins regulated in BJF-treated rat lung tissues.

Mentions: Initially we explored the biological functions of the overlapping proteins between potential targets of BJF and transcripts in BJF-treated rats. The result showed that 11 overlapping proteins (ACACA, ampC, APP, BCL2, CDK2, FASN, gyrB, katA, KCNH2, MAPK3, and NR3C1) were related to many different biological functions including oxidoreductase activity, MAP kinase activity, and NF-kappa-B binding (Figure 11(a)). Next, 9 overlapping proteins (ATP5B, CALM1, COL1A1, HBB, HSPA5, MGC72973, SOD1, LOC100134871, and LOC689064) between the system pharmacology targets and proteins regulated in BJF-treated rats were identified. The molecular functions of the 9 proteins were mainly related to oxidoreductase, antioxidant, superoxide dismutase activity, and ATPase activity (Figure 11(b)). Furthermore, the potential relationships of target proteins and metabolites regulated in BJF-treated rats were analyzed. In Figure 12, the results showed that metabolite-target protein network mainly contained lipid metabolism.


Integrating Transcriptomics, Proteomics, and Metabolomics Profiling with System Pharmacology for the Delineation of Long-Term Therapeutic Mechanisms of Bufei Jianpi Formula in Treating COPD
Overlapping proteins' molecular functions. BiNGO was applied to analyze the molecular functions of the overlapping proteins. (a) Molecular function analysis of overlapping proteins between the system pharmacology targets and transcript measurements in lung tissues BJF-treated rats. (b) Molecular function analysis of overlapping proteins between the potential targets and proteins regulated in BJF-treated rat lung tissues.
© Copyright Policy
Related In: Results  -  Collection

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

fig11: Overlapping proteins' molecular functions. BiNGO was applied to analyze the molecular functions of the overlapping proteins. (a) Molecular function analysis of overlapping proteins between the system pharmacology targets and transcript measurements in lung tissues BJF-treated rats. (b) Molecular function analysis of overlapping proteins between the potential targets and proteins regulated in BJF-treated rat lung tissues.
Mentions: Initially we explored the biological functions of the overlapping proteins between potential targets of BJF and transcripts in BJF-treated rats. The result showed that 11 overlapping proteins (ACACA, ampC, APP, BCL2, CDK2, FASN, gyrB, katA, KCNH2, MAPK3, and NR3C1) were related to many different biological functions including oxidoreductase activity, MAP kinase activity, and NF-kappa-B binding (Figure 11(a)). Next, 9 overlapping proteins (ATP5B, CALM1, COL1A1, HBB, HSPA5, MGC72973, SOD1, LOC100134871, and LOC689064) between the system pharmacology targets and proteins regulated in BJF-treated rats were identified. The molecular functions of the 9 proteins were mainly related to oxidoreductase, antioxidant, superoxide dismutase activity, and ATPase activity (Figure 11(b)). Furthermore, the potential relationships of target proteins and metabolites regulated in BJF-treated rats were analyzed. In Figure 12, the results showed that metabolite-target protein network mainly contained lipid metabolism.

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.