System biology analysis of long-term effect and mechanism of Bufei Yishen on COPD revealed by system pharmacology and 3-omics profiling.

Jiansheng Li,Liping Yang,Yange Tian,Suyun Li,Ya Li,Peng Zhao

doi:10.1038/srep25492

Jiansheng Li, Liping Yang + Show 4 more

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https://doi.org/10.1038/srep25492

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Abstract

System pharmacology identified 195 potential targets of Bufei Yishen formula (BYF), and BYF was proven to have a short-term therapeutic effect on chronic obstructive pulmonary disease (COPD) rats previously. However, the long-term effect and mechanism of BYF on COPD is still unclear. Herein, we explored its long-term effect and underlying mechanism at system level. We administered BYF to COPD rats from week 9 to 20, and found that BYF could prevent COPD by inhibiting the inflammatory cytokines expression, protease-antiprotease imbalance and collagen deposition on week 32. Then, using transcriptomics, proteomics and metabolomics analysis, we identified significant regulated genes, proteins and metabolites in lung tissues of COPD and BYF-treated rats, which could be mainly attributed to oxidoreductase-antioxidant activity, focal adhesion, tight junction or lipid metabolism. Finally, based on the comprehensive analysis of system pharmacology target, transcript, protein and metabolite data sets, we found a number of genes, proteins, metabolites regulated in BYF-treated rats and the target proteins of BYF were involved in lipid metabolism, inflammatory response, oxidative stress and focal adhension. In conclusion, BYF exerts long-term therapeutic action on COPD probably through modulating the lipid metabolism, oxidative stress, cell junction and inflammatory response pathways at system level.

Highlights

Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by progressive airflow limitation and is thought to result in part from exaggerated pulmonary inflammation in response to chronic aero-pollutant exposure, primarily from smoking[1]
Lung injury scores, bronchiole wall thickness, small pulmonary vessels wall thickness, bronchiole stenosis, and alveolar diameter increased in the model rat, which could be significantly suppressed by the treatment of animals with Bufei Yishen formula (BYF) (Fig. 2A–F)
In system pharmacology and in vivo experimental study, we showed that MAPK1/3 (ERK1/2), MAPK14 (p38), MAPK8 (JNK) and NF-κ B were the potential targets of BYF, and inflammatory cytokines, including IL-1β, IL-6 and tumor necrosis factor (TNF)-α were suppressed by BYF treatment

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by progressive airflow limitation and is thought to result in part from exaggerated pulmonary inflammation in response to chronic aero-pollutant exposure, primarily from smoking[1]. We conducted a systems-level analysis of the long-term therapeutic effect and underlying mechanism of BYF, which could provide more system experimental evidences to validate the system pharmacology predictions. The transcriptomics- proteomics- metabolomics-profiling-technologies integrate the entirety of the biological complement to propose a system-level way of study TCM formula in the form of systems biology[9,10,11]. Comprehensive analyses of the system pharmacology, transcriptomics, proteomics and metabolomics datasets have the potential to provide a system-wide view of the complex biological processes and the function of the multiple compounds contained in TCM formula. We integrated system pharmacology, transcriptomics, proteomics and metabolomics data streams to provide a system picture of the long-term mechanisms of BYF in treating COPD rats

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