title: Systems pharmacology-based approach for dissecting the active ingredients and potential targets of the Chinese herbal Bufei Jianpi formula for the treatment of COPD.
abstract: BACKGROUND
  The Chinese herbal Bufei Jianpi formula (BJF) provides an effective treatment option for chronic obstructive pulmonary disease (COPD). However, the systems-level mechanism underlying the clinical effects of BJF on COPD remains unknown.
  
  
  METHODS
  In this study, a systems pharmacology model based on absorption filtering, network targeting, and systems analyses was applied specifically to clarify the active compounds and therapeutic mechanisms of BJF. Then, a rat model of cigarette smoke- and bacterial infection-induced COPD was used to investigate the therapeutic mechanisms of BJF on COPD and its comorbidity.
  
  
  RESULTS
  The pharmacological system successfully identified 145 bioactive ingredients from BJF and revealed 175 potential targets. There was a significant target overlap between the herbal constituents of BJF. These results suggested that each herb of BJF connected with similar multitargets, indicating potential synergistic effects among them. The integrated target-disease network showed that BJF probably was efficient for the treatment of not only respiratory tract diseases but also other diseases, such as nervous system and cardiovascular diseases. The possible mechanisms of action of BJF were related to activation of inflammatory response, immune responses, and matrix metalloproteinases, among others. Furthermore, we demonstrated that BJF treatment could effectively prevent COPD and its comorbidities, such as ventricular hypertrophy, by inhibition of inflammatory cytokine production, matrix metalloproteinases expression, and other cytokine production in vivo.
  
  
  CONCLUSIONS
  This study using the systems pharmacology method, in combination with in vivo experiments, helped us successfully dissect the molecular mechanism of BJF for the treatment of COPD and predict the potential targets of the multicomponent BJF, which provides a new approach to illustrate the synergetic mechanism of the complex prescription and discover more effective drugs against COPD.
authors.affiliation: Key Laboratory of Chinese Internal Medicine, Henan University of Traditional Chinese Medicine, People's Republic of China ; Key Laboratory of Chinese Internal Medicine, Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, Zhengzhou, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Chinese Internal Medicine, Henan University of Traditional Chinese Medicine, People's Republic of China ; Key Laboratory of Chinese Internal Medicine, Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, Zhengzhou, People's Republic of China.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Chinese Internal Medicine, Henan University of Traditional Chinese Medicine, People's Republic of China ; Key Laboratory of Chinese Internal Medicine, Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, Zhengzhou, People's Republic of China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Chinese Internal Medicine, Henan University of Traditional Chinese Medicine, People's Republic of China ; Key Laboratory of Chinese Internal Medicine, Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, Zhengzhou, People's Republic of China.
authors.forename: Yange
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Key Laboratory of Chinese Internal Medicine, Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment and Chinese Medicine Development of Henan Province, Zhengzhou, People's Republic of China ; Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, People's Republic of China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, People's Republic of China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000032:analysis / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000032:analysis / Q000494:pharmacology*; D005260:Female; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000382:microbiology / Q000503:physiopathology; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors / Q000032:analysis / Q000494:pharmacology*; D008516:Medicine, Chinese Traditional; D008517:Phytotherapy; D010946:Plants, Medicinal; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000382:microbiology / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000009:adverse effects; D049490:Systems Biology / Q000379:methods*; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D018836:Inflammation Mediators; D061965:Matrix Metalloproteinase Inhibitors; C000610679:bufei jianpi
keywords: Bufei Jianpi formula; chronic obstructive pulmonary disease; systems pharmacology