title: Network pharmacology-based prediction and verification of the molecular targets and pathways for schisandrin against cerebrovascular disease.
abstract: OBJECTIVE
  To illuminate the molecular targets for schisandrin against cerebrovascular disease based on the combined methods of network pharmacology prediction and experimental verification.
  
  
  METHODS
  A protein database was established through constructing the drug-protein network from literature mining data. The protein-protein network was built through an in-depth exploration of the relationships between the proteins. The computational platform was implemented to predict and extract the sensitive sub-network with significant P-values from the protein-protein network. Then the key targets and pathways were identified from the sensitive sub-network. The most related targets and pathways were also confirmed in hydrogen peroxide (H2O2)-induced PC12 cells by Western blotting.
  
  
  RESULTS
  Twelve differentially expressed proteins (gene names: NFKB1, RELA, TNFSF10, MAPK1, CHUK, CASP8, PIGS2, MAPK14, CREB1, IFNG, APP, and BCL2) were confirmed as the central nodes of the interaction network (45 nodes, 93 edges). The NF-κB signaling pathway was suggested as the most related pathway of schisandrin for cerebrovascular disease. Furthermore, schisandrin was found to suppress the expression and phosphorylation of IKKα, as well as p50 and p65 induced by H2O2 in PC12 cells by Western blotting.
  
  
  CONCLUSIONS
  The computational platform that integrates literature mining data, protein-protein interactions, sensitive sub-network, and pathway results in identification of the NF-κB signaling pathway as the key targets and pathways for schisandrin.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China; Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Yan-Ni
authors.initials: YN
authors.lastname: Lv
authors.affiliation: Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Shao-Xia
authors.initials: SX
authors.lastname: Li
authors.affiliation: Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Ke-Feng
authors.initials: KF
authors.lastname: Zhai
authors.affiliation: Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China. Electronic address: junpingkou@163.com.
authors.forename: Jun-Ping
authors.initials: JP
authors.lastname: Kou
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China. Electronic address: boyangyu59@163.com.
authors.forename: Bo-Yang
authors.initials: BY
authors.lastname: Yu
mesh_terms: D000818:Animals; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D034242:Cyclooctanes / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D053263:Gene Regulatory Networks / Q000187:drug effects*; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D058990:Molecular Targeted Therapy; D016716:PC12 Cells; D011083:Polycyclic Compounds / Q000494:pharmacology*; D060066:Protein Interaction Maps / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D034242:Cyclooctanes; D004365:Drugs, Chinese Herbal; D017705:Lignans; D011083:Polycyclic Compounds; C011105:schizandrin
keywords: Cerebrovascular disease; Molecular target; NF-κB signaling pathway; Network pharmacology; Schisandrin