title: Qingnaoyizhi decoction suppresses the formation of glial fibrillary acidic protein-positive cells in cultured neural stem cells by inhibiting the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway.
abstract: OBJECTIVE
  Inactivation of the Janus kinase 2 in treated NSCs. Furthermore, QNYZD may play a direct role in suppressing the formation of GFAP-positive cells and enhancing neuronal differentiation by inhibiting JAK2/STAT3 activation. Overall, these results provide insights into the possible mechanism underlying QNYZD-mediated neurogenesis. (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling axis plays a crucial role in determining the fate of neural stem cells (NSCs). Qingnaoyizhi decoction (QNYZD) has been used for the treatment of vascular dementia and has shown to improve synaptic remodeling. The aim of this study was to evaluate the effect of cerebrospinal fluid (CSF) containing QNYZD (CSF-QNYZD) on the differentiation of cultured NSCs and the involvement of the JAK2/STAT3 pathway.
  
  
  METHODS
  The protein expression levels of glial fibrillary acidic protein (GFAP), tubulin, drosophila mothers against decapentaplegic protein (SMAD-1), STAT3, and phosphorylated-STAT3 were detected by western immunoblot analysis in the groups: control, CSF, JAK/STAT inhibitor (AG490), CSF-QNYZD, and CSF-XDZ (CSF-Xidezhen). The differentiation of NSCs was determined by immunofluorescence staining. The proliferation of NSCs was measured using the Cell Counting Kit-8 proliferation assay.
  
  
  RESULTS
  Compared with the control group, CSF-QNYZD and AG490 significantly increased the number and expression of tubulin-positive cells, reduced the number and expression of GFAP-positive cells, and down-regulated the expression of p-STAT3. However, CSF-QNYZD also decreased the expression of SMAD-1 and STAT3.
  
  
  CONCLUSIONS
  Enhanced neuronal differentiation may be associated with the down-regulation of glial differentiation instead of promoting proliferation in treated NSCs. Furthermore, QNYZD may play a direct role in suppressing the formation of GFAP-positive cells and enhancing neuronal differentiation by inhibiting JAK2/STAT3 activation. Overall, these results provide insights into the possible mechanism underlying QNYZD-mediated neurogenesis.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Wu
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Jing
authors.forename: Xiude
authors.initials: X
authors.lastname: Qin
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhou
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Wanshan
authors.initials: W
authors.lastname: Song
authors.forename: Xueyan
authors.initials: X
authors.lastname: Wang
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Hou
authors.forename: Yulian
authors.initials: Y
authors.lastname: Zhang
authors.forename: Liyuan
authors.initials: L
authors.lastname: Kang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D004365:Drugs, Chinese Herbal; D005904:Glial Fibrillary Acidic Protein; D050796:STAT3 Transcription Factor; D053614:Janus Kinase 2