Systems pharmacology-based dissection of mechanisms of Chinese medicinal formula Bufei Yishen as an effective treatment for chronic obstructive pulmonary disease.

Jiansheng Li,Peng Zhao,Yange Tian,Yonghua Wang,Ya Li

doi:10.1038/srep15290

Abstract

The present work adopted a systems pharmacology-based approach to provide new insights into the active compounds and therapeutic targets of Bufei Yishen formula (BYF) for the treatment of chronic obstructive pulmonary disease (COPD). In addition, we established a rat model of cigarette smoke- and bacterial infection-induced COPD to validate the mechanisms of BYF action that were predicted in systems pharmacology study. The systems pharmacology model derived 216 active compounds from BYF and 195 potential targets related to various diseases. The compound-target network showed that each herbal drug in the BYF formula acted on similar targets, suggesting potential synergistic effects among these herbal drugs. The ClueGo assay, a Cytoscape plugin, revealed that most targets were related to activation of MAP kinase and matrix metalloproteinases. By using target-diseases network analysis, we found that BYF had great potential to treatment of multiple diseases, such as respiratory tract diseases, immune system, and cardiovascular diseases. Furthermore, we found that BYF had the ability to prevent COPD and its comorbidities, such as ventricular hypertrophy, in vivo. Moreover, BYF inhibited the inflammatory cytokine, and hypertrophic factors expression, protease-antiprotease imbalance and the collagen deposition, which may be the underlying mechanisms of action of BYF.

Highlights

The present work adopted a systems pharmacology-based approach to provide new insights into the active compounds and therapeutic targets of Bufei Yishen formula (BYF) for the treatment of chronic obstructive pulmonary disease (COPD)
Much effort has been made in clarifying the therapeutic mechanism of action of traditional Chinese medicines (TCM), but complex chemical composition of TCM makes it hard to understand its mechanism from a molecular level
We demonstrated that BYF provided protective and therapeutic benefits against cigarette smoke- and bacterial infection-induced pulmonary inflammation, collagen deposition, protease-antiprotease imbalance and hypertrophic factors production, suggesting that this formula could be effective for the treatment of COPD and its comorbidity, ventricular hypertrophy

Summary

Introduction

The present work adopted a systems pharmacology-based approach to provide new insights into the active compounds and therapeutic targets of Bufei Yishen formula (BYF) for the treatment of chronic obstructive pulmonary disease (COPD). Systems pharmacology is an emerging field that combines oral bioavailability prediction, multiple drug targets prediction and network analysis to understand the active compounds and therapeutic targets of TCM7–9. We proposed a systems pharmacology approach to investigate the pharmacological mechanisms of action and active substances of BYF by systematically incorporating active compounds prediction, therapeutic targets prediction, and drug-target-disease network analysis.

Results

Conclusion