title: An integrated pathway interaction network for the combination of four effective compounds from ShengMai preparations in the treatment of cardio-cerebral ischemic diseases.
abstract: OBJECTIVE
  SMXZF (a combination of ginsenoside Rb1, ginsenoside Rg1, schizandrin and DT-13) derived from Chinese traditional medicine formula ShengMai preparations) is capable of alleviating cerebral ischemia-reperfusion injury in mice. In this study we used network pharmacology approach to explore the mechanisms of SMXZF in the treatment of cardio-cerebral ischemic diseases.
  
  
  METHODS
  Based upon the chemical predictors, such as chemical structure, pharmacological information and systems biology functional data analysis, a target-pathway interaction network was constructed to identify potential pathways and targets of SMXZF in the treatment of cardio-cerebral ischemia. Furthermore, the most related pathways were verified in TNF-α-treated human vascular endothelial EA.hy926 cells and H2O2-treated rat PC12 cells.
  
  
  RESULTS
  Three signaling pathways including the NF-κB pathway, oxidative stress pathway and cytokine network pathway were demonstrated to be the main signaling pathways. The results from the gene ontology analysis were in accordance with these signaling pathways. The target proteins were found to be associated with other diseases such as vision, renal and metabolic diseases, although they exerted therapeutic actions on cardio-cerebral ischemic diseases. Furthermore, SMXZF not only dose-dependently inhibited the phosphorylation of NF-κB, p50, p65 and IKKα/β in TNF-α-treated EA.hy926 cells, but also regulated the Nrf2/HO-1 pathway in H2O2-treated PC12 cells.
  
  
  CONCLUSIONS
  NF-κB signaling pathway, oxidative stress pathway and cytokine network pathway are mainly responsible for the therapeutic actions of SMXZF against cardio-cerebral ischemic diseases.
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Yan-ni
authors.initials: YN
authors.lastname: Lv
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Yi-sha
authors.initials: YS
authors.lastname: Tan
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Shen
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Ke-feng
authors.initials: KF
authors.lastname: Zhai
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Jun-ping
authors.initials: JP
authors.lastname: Kou
authors.affiliation: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Bo-yang
authors.initials: BY
authors.lastname: Yu
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D034242:Cyclooctanes / Q000494:pharmacology*; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D011083:Polycyclic Compounds / Q000494:pharmacology*; D060066:Protein Interaction Maps / Q000187:drug effects; D051381:Rats; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D049490:Systems Biology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D034242:Cyclooctanes; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D017705:Lignans; D016328:NF-kappa B; D011083:Polycyclic Compounds; D012503:Saponins; D014409:Tumor Necrosis Factor-alpha; C009252:fructus schizandrae, radix ginseng, radix ophiopogonis drug combination; C578958:ruscogenin-1-O-(glucopyranosyl-(1-2))(xylopyranosyl-(1-3))fucopyranoside; C442759:ginsenoside Rb1; C011105:schizandrin; C035054:ginsenoside Rg1