title: An integrated global chemomics and system biology approach to analyze the mechanisms of the traditional Chinese medicinal preparation Eriobotrya japonica - Fritillaria usuriensis dropping pills for pulmonary diseases.
abstract: BACKGROUND
  Traditional Chinese medicine (TCM) herbal formulae provide valuable therapeutic strategies. However, the active ingredients and mechanisms of action remain unclear for most of these formulae. Therefore, the identification of complex mechanisms is a major challenge in TCM research.
  
  
  METHODS
  This study used a network pharmacology approach to clarify the anti-inflammatory and cough suppressing mechanisms of the Chinese medicinal preparation Eriobotrya japonica - Fritillaria usuriensis dropping pills (ChuanbeiPipa dropping pills, CBPP). The chemical constituents of CBPP were identified by high-quality ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS), and anti-inflammatory ingredients were selected and analyzed using the PharmMapper and Kyoto Encyclopedia of Genes and Genomes (KEGG) bioinformatics websites to predict the target proteins and related pathways, respectively. Then, an RNA-sequencing (RNA-Seq) analysis was carried out to investigate the different expression of genes in the lung tissue of rats with chronic bronchitis.
  
  
  RESULTS
  Six main constituents affected 19 predicted pathways, including ursolic acid and oleanolic acid from Eriobotrya japonica (Thunb.) Lindl. (Eri), peiminine from Fritillaria usuriensis Maxim. (Fri), platycodigenin and polygalacic acid from Platycodon grandiflorum (Jacq.) A. DC. (Pla) and guanosine from Pinellia ternata (Thunb.) Makino. (Pin). Expression of 34 genes was significantly decreased after CBPP treatment, affecting four therapeutic functions: immunoregulation, anti-inflammation, collagen formation and muscle contraction.
  
  
  CONCLUSIONS
  The active components acted on the mitogen activated protein kinase (MAPK) pathway, transforming growth factor (TGF)-beta pathway, focal adhesion, tight junctions and the action cytoskeleton to exert anti-inflammatory effects, resolve phlegm, and relieve cough. This novel approach of global chemomics-integrated systems biology represents an effective and accurate strategy for the study of TCM with multiple components and multiple target mechanisms.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300071, People's Republic of China. taojin@nankai.edu.cn.|Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300071, People's Republic of China. taojin@nankai.edu.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Tao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300071, People's Republic of China. houyy@nankai.edu.cn.|Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300071, People's Republic of China. houyy@nankai.edu.cn.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300071, People's Republic of China. mxy83396376@163.com.|Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300071, People's Republic of China. mxy83396376@163.com.
authors.forename: Xiaoyao
authors.initials: X
authors.lastname: Ma
authors.affiliation: No.6 TCM Factory, Zhongxin Pharmaceuticals, Tianjin, 300193, People's Republic of China. tjliudan@sina.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: No.6 TCM Factory, Zhongxin Pharmaceuticals, Tianjin, 300193, People's Republic of China. cherries0716@sina.com.
authors.forename: Yongling
authors.initials: Y
authors.lastname: Tong
authors.affiliation: No.6 TCM Factory, Zhongxin Pharmaceuticals, Tianjin, 300193, People's Republic of China. 799660790@qq.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300071, People's Republic of China. ahbbgaojie@yahoo.com.cn.|Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300071, People's Republic of China. ahbbgaojie@yahoo.com.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300071, People's Republic of China. gangbai@nankai.edu.cn.|Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300071, People's Republic of China. gangbai@nankai.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Bai
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D029481:Bronchitis, Chronic / Q000188:drug therapy* / Q000235:genetics; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000627:therapeutic use*; D031983:Eriobotrya / Q000737:chemistry*; D031410:Fritillaria / Q000737:chemistry*; D015870:Gene Expression; D008516:Medicine, Chinese Traditional; D051381:Rats; D017207:Rats, Sprague-Dawley; D017423:Sequence Analysis, RNA; D015398:Signal Transduction / Q000187:drug effects; D049490:Systems Biology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004365:Drugs, Chinese Herbal