Hierarchical profiles of signaling pathways and networks reveal two complementary pharmacological mechanisms

Yinying Chen, Fanyun Meng, Hong Fang, Yanan Yu, Jun Liu, Zhiwei Jing, Aiping LYU, Zhong Wang*, Yongyan Wang

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

11 Citations (Scopus)


Until now the overlapping and diverse pharmacological protective mechanisms of different compounds in the treatment of cerebral ischemia, both on the signaling pathway and network levels have not been revealed. In order to find differential pathway networks from gene expression profiles of hippocampus of ischemic mice treated with baicalin (BA), ursodeoxycholic acid (UA) and jasminoidin (JA), a microarray comprising 16,463 genes, FDA Arraytrack software and Ingenuity Pathway Analysis, was employed. A total of 5, 8, 11, 9 networks and 6, 7, 40, 16 pathways were found in vehicle (vs sham), BA, UA and JA (vs vehicle), respectively. Only 4 and 7 overlapping pathways were shared between BA and UA, UA and JA, accounting for 9.3% and 14.3% of the total number of all pathways, respectively. BA, UA and JA all acted on Ca2+-dependent signaling cascades in diverse links. BA intervened in arachidonic acid metabolism. UA affected eicosanoid, cyclin-dependent kinase 5, nuclear factor-κB, and T-helper 1 cell cytokine production. It was found that JA might decrease oxidative damage via nuclear factor erythroid 2-related factor 2-mediated antioxidant response. Compared to vehicle, no overlapping pathways were found among three groups. However, the total of 60 (71.4%) overlapping functions could be approximately divided into diseases and disorders, molecular and cellular functions, physiological system development and function as categories with ratio of 1:1:1. Analysis of network functions and known pathways may be two complementary paradigms for revealing potential pharmacological mechanisms based on the same phenotype variation.

Original languageEnglish
Pages (from-to)882-893
Number of pages12
JournalCNS and Neurological Disorders - Drug Targets
Issue number6
Publication statusPublished - 2013

Scopus Subject Areas

  • Neuroscience(all)
  • Pharmacology

User-Defined Keywords

  • Cerebral ischemia
  • Ingenuity Pathway Analysis
  • Networks function
  • Pharmacological mechanism
  • Signaling pathway


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